| 1. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 3. |
- B. Moreno, Anaísa
(författare)
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Evolution and host-specific adaptations of Legionella pneumophila
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- How bacteria evolve pathogenic traits is shaped by their communities and environments. Legionella pneumophila is ubiquitous in aquatic habitats, where it persists by replicating within a broad range of protozoan hosts. Using the same mechanisms, L. pneumophila may also accidentally infect humans, causing a severe pneumonia known as Legionnaires’ disease. As hosts, humans are evolutionary dead-ends, resulting in the loss of human-specific adaptations after infection. This thesis aims to identify and characterise these host adaptations.In Paper I, we study the in-patient evolution of L. pneumophila. We collected a large set of strains from sporadic infections and outbreaks, pairing clinical isolates with their respective environmental sources. Using comparative genomic analyses, we identified two genes individually mutated in three independent infections. One gene encoded an outer membrane protein, a homolog from the OmpP1/FadL family, and the other an EAL domain-containing protein. These results suggest that convergent evolution may be at play and that these mutations are potential candidates for human-specific host adaptations.In Paper II, we investigate host adaptation and the selective pressures that drive it using a long-term experimental evolution approach. We passaged L. pneumophila in Acanthamoeba castellanii and U937 macrophages, separately and in alternation, for over 800 generations. We found 49 fixed mutations across the 18 evolved populations: two distinct mutations in RpsL, which confers streptomycin resistance, as well as two additional mutations, each consistently associated with one of the former, in the chaperonin GroES or in RpsD, a known compensatory mutation. Mutations in the lipopolysaccharide synthesis operon were observed only in lineages passaged in A. castellanii, whilst mutations in LerC were fixed in six lineages passaged in U937, making these candidate mutations for host-specific adaptations.In Paper III, we shift focus to A. castellanii, a natural host of L. pneumophila. We describe a novel method for high-efficiency transfection of this amoeba with a cationic polymer. Using a systematic approach to test different parameters, we found that widely available and inexpensive polyethylenimines can be used to transfect A. castellanii at a much greater efficiency than the currently used reagents.In conclusion, these studies suggest that although L. pneumophila can infect humans, it is sub-optimally adapted for it, and offer potential determinants of host-specificity in L. pneumophila.
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| 4. |
- Brandis, Gerrit, 1985-, et al.
(författare)
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Expression of the qepA1 gene is induced under antibiotic exposure
- 2021
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 76:6, s. 1433-1440
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe qepA1 gene encodes an efflux pump that reduces susceptibility to ciprofloxacin. Little is known about the regulation of qepA1 expression.ObjectivesTo assess the potential role of ciprofloxacin and other antibiotics in the regulation of qepA1 gene expression. To identify the promoter that drives qepA1 expression and other factors involved in expression regulation. To assess whether the identified features are universal among qepA alleles.MethodsA translational qepA1-yfp fusion under the control of the qepA1 upstream region was cloned into the Escherichia coli chromosome. Expression of the fusion protein was measured in the presence of various antibiotics. Deletions within the upstream region were introduced to identify regions involved in gene expression and regulation. The qepA1 coding sequence and upstream region were compared with all available qepA sequences.ResultsCellular stress caused by the presence of various antibiotics can induce qepA1 expression. The qepA1 gene is fused to a class I integron and gene expression is driven by the Pc promoter within the integrase gene. A segment within the integron belonging to a truncated dfrB4 gene is essential for the regulation of qepA1 expression. This genetic context is universal among all sequenced qepA alleles.ConclusionsThe fusion of the qepA1 gene to a class I integron has created a novel regulatory unit that enables qepA1 expression to be under the control of antibiotic exposure. This setup mitigates potential negative effects of QepA1 production on bacterial fitness by restricting high-level expression to environmental conditions in which QepA1 is beneficial.
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| 5. |
- Delgado, Luis Fernando
(författare)
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Bioinformatics for microbiome analysis
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Marine ecosystems harbour a vast microbial diversity which play a crucial role in ecosystemfunctioning. Advancements in DNA sequencing technologies have transformed our ability to analyse microbial populations comprehensively. Metagenomic sequencing has emerged as a pivotal tool for characterising microbial communities across various environments. Bioinformatics, an interdisciplinary field, facilitates the analysis and interpretation of large biological datasets, including microbiome data.This thesis aims to enhance bioinformatics approaches for analysing marine microbiomes. It comprises four papers covering bioinformatic developments and genomic data analysis across multiple topics, including metagenomics, pangenomics, comparative genomics and population genomics:Paper I evaluated three assembly strategies for constructing gene catalogues from metagenomic samples: individual sample assembly with gene clustering, co-assembly of all samples, and a new hybrid approach, mix assembly. The efficacy of the mix-assembly approach was highlighted for maximising information extraction from metagenomic samples, offering opportunities for further exploration in microbial ecology and environmental genomics.Using the mix-assembly approach, we conducted a comprehensive analysis of 124 metagenomic samples sourced from the Baltic Sea, resulting in the refinement of the Baltic Sea Gene Set (BAGS v1.1), which now encompasses 66.53 million genes annotated for both functionality and taxonomy. In Paper II, we introduced an open-access initiative that provided the mix-assembly pipeline code. We also developed the BAGS-Shiny web application to facilitate user interaction with this extensive gene catalogue.Paper III focused on whole-genome sequencing and assembly of 82 environmental V. vulnificus strains from the Baltic Sea, enabling comprehensive comparative genomic analysis. I developed the PhyloBOTL pipeline, which uses a phylogeny-based approach to identify genes associated with pathogenicity. Comparative genomics of 208 clinical isolates and 199 environmental isolates revealed 58 enriched orthologs in pathogenic strains, including known virulence factors and novel genes. Potential biomarkers for pathogenic V. vulnificus were identified, and primers suitable for PCR-based environmental monitoring were designed (in silico).In Paper IV population genomics analysis was carried out, using the Input_Pogenom pipeline and POGENOM tool, to explore intraspecific biogeographical patterns. Geographical barriers were found to significantly influence aquatic bacteria distribution, with greater genetic differentiation observed between Baltic and Caspian seas than within the Baltic Sea's salinity gradient.
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| 6. |
- Fer, Evrim, et al.
(författare)
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Early divergence of translation initiation and elongation factors
- 2022
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Ingår i: Protein Science. - : John Wiley & Sons. - 0961-8368 .- 1469-896X. ; 31:9
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Tidskriftsartikel (refereegranskat)abstract
- Protein translation is a foundational attribute of all living cells. The translation function carried out by the ribosome critically depends on an assortment of protein interaction partners, collectively referred to as the translation machinery. Various studies suggest that the diversification of the translation machinery occurred prior to the last universal common ancestor, yet it is unclear whether the predecessors of the extant translation machinery factors were functionally distinct from their modern counterparts. Here we reconstructed the shared ancestral trajectory and subsequent evolution of essential translation factor GTPases, elongation factor EF-Tu (aEF-1A/eEF-1A), and initiation factor IF2 (aIF5B/eIF5B). Based upon their similar functions and structural homologies, it has been proposed that EF-Tu and IF2 emerged from an ancient common ancestor. We generated the phylogenetic tree of IF2 and EF-Tu proteins and reconstructed ancestral sequences corresponding to the deepest nodes in their shared evolutionary history, including the last common IF2 and EF-Tu ancestor. By identifying the residue and domain substitutions, as well as structural changes along the phylogenetic history, we developed an evolutionary scenario for the origins, divergence and functional refinement of EF-Tu and IF2 proteins. Our analyses suggest that the common ancestor of IF2 and EF-Tu was an IF2-like GTPase protein. Given the central importance of the translation machinery to all cellular life, its earliest evolutionary constraints and trajectories are key to characterizing the universal constraints and capabilities of cellular evolution.
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| 7. |
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| 8. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 9. |
- Garmendia, Eva, et al.
(författare)
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Chromosomal Location Determines the Rate of Intrachromosomal Homologous Recombination in Salmonella
- 2021
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- Homologous recombination is an important mechanism directly involved in the repair, organization, and evolution of prokaryotic and eukaryotic chromosomes. We developed a system, based on two genetic cassettes, that allows the measurement of recombinational repair rates between different locations on the chromosome. Using this system, we analyzed 81 different positional combinations throughout the chromosome to answer the question of how the position and orientation of sequences affect intrachromosomal homologous recombination. Our results show that recombination was possible between any two locations tested in this study and that recombinational repair rates varied by just above an order of magnitude. The observed differences in rate do not correlate with distance between the recombination cassettes or with distance from the origin of replication but could be explained if each location contributes individually to the recombination event. The relative levels of accessibility for recombination vary 5-fold between the various cassette locations, and we found that the nucleoid structure of the chromosome may be the major factor influencing the recombinational accessibility of each chromosomal site. Furthermore, we found that the orientation of the recombination cassettes had a significant impact on recombination. Recombinational repair rates for the cassettes inserted as direct repeats are, on average, 2.2-fold higher than those for the same sets inserted as inverted repeats. These results suggest that the bacterial chromosome is not homogenous with regard to homologous recombination, with regions that are more or less accessible, and that the orientation of genes affects recombination rates. IMPORTANCE Bacterial chromosomes frequently carry multiple copies of genes at separate chromosomal locations. In Salmonella, these include the 7 rrn operons and the duplicate tuf genes. Genes within these families coevolve by homologous recombination, but it is not obvious whether their rates of recombination reflect general rates of intrachromosomal recombination or are an evolved property particularly associated with these conserved genes and locations. Using a novel experimental system, we show that recombination is possible between all tested pairs of locations at rates that vary by just above 1 order of magnitude. Differences in rate do not correlate with distance between the sites or distance to the origin of replication but may be explained if each location contributes individually to the recombination event. Our results suggest the existence of bacterial chromosomal domains that are differentially available for recombination and that gene orientation affects recombination rates.
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| 10. |
- Graells, Tiscar, et al.
(författare)
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Legionella pneumophila recurrently isolated in a Spanish hospital : Two years of antimicrobial resistance surveillance
- 2018
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 166, s. 638-646
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to monitor the spread, persistence and antibiotic resistance patterns of Legionella spp. strains found in a hospital water distribution system. These environmental studies are intended to help detect the presence of antibiotic resistant strains before they infect patients.METHODS: Antimicrobial surveillance tests were performed at 27 different sampling points of the water network of a large Spanish hospital over two years. Water samples were screened for Legionella according to ISO 11731:2007. Legionella spp. isolates were identified by serotyping and by mass spectrometry (MALDI-ToF). Epidemiological molecular typing was done by Pulse-Field Gel Electrophoresis (PFGE) and by Sequence-Based Typing (SBT). Antibiotic susceptibility tests were performed using disk diffusion and ETEST®.RESULTS: Legionella spp. were recurrently isolated for 2 years. All isolates belonged the same group, L. pneumophila serogroups 2-14. Isolates were all attributed by SBT to sequence type (ST) ST328, although PFGE revealed 5 different patterns. No significant change in antibiotic susceptibility could be observed for this study period, irrespectively of the method used.CONCLUSION: Colonization of water systems by Legionella spp. is still occurring, although all the prevention rules were strictly followed. Antibiotic resistance monitoring may help us to find resistance in bacteria with environmental reservoirs but difficult to isolate from patients. The knowledge of the antibiotic susceptibility in environmental strains may help us to predict changes in clinical strains. This study might also help reconsidering Legionnaires' disease (LD) diagnostic methods. L. pneumophila serogroups 2-14 present all along the time of the investigation in the water distribution system can cause LD. However, they may not be detected by routine urine tests run on patients, thereby missing an ongoing LD infection.
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| 11. |
- Graells, Tiscar, et al.
(författare)
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The all-intracellular order Legionellales is unexpectedly diverse, globally distributed and lowly abundant.
- 2018
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Ingår i: FEMS Microbiology Ecology. - : Oxford University Press. - 0168-6496 .- 1574-6941. ; 94:12
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Tidskriftsartikel (refereegranskat)abstract
- Legionellales is an order of the Gammaproteobacteria, only composed of host-adapted, intracellular bacteria, including the accidental human pathogens Legionella pneumophila and Coxiella burnetii. Although the diversity in terms of lifestyle is large across the order, only a few genera have been sequenced, owing to the difficulty to grow intracellular bacteria in pure culture. In particular, we know little about their global distribution and abundance.Here, we analyze 16/18S rDNA amplicons both from tens of thousands of published studies and from two separate sampling campaigns in and around ponds and in a silver mine. We demonstrate that the diversity of the order is much larger than previously thought, with over 450 uncultured genera. We show that Legionellales are found in about half of the samples from freshwater, soil and marine environments, and quasi-ubiquitous in man-made environments. Their abundance is low, typically 0.1%, with few samples up to 1%. Most Legionellales OTUs are globally distributed, while many do not belong to a previously identified species.This study sheds a new light on the ubiquity and diversity of one major group of host-adapted bacteria. It also emphasizes the need to use metagenomics to better understand the role of host-adapted bacteria in all environments.
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| 12. |
- Guy, Lionel, et al.
(författare)
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A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen Bartonella
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:3, s. e1003393-
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Tidskriftsartikel (refereegranskat)abstract
- Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial genome. A novel putative GTA was recently discovered in the mouse-infecting bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. Here, we present a comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size, including six novel genomes from Bartonella isolated from a cow, two moose, two dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core genes indicates that the deadly human pathogen B. bacilliformis is related to the ruminant-adapted clade, rather than being the earliest diverging species in the genus as previously thought. A gene flux analysis identified 12 genes for a GTA and a phage-derived origin of replication as the most conserved innovations. These are located in a region of a few hundred kb that also contains 8 insertions of gene clusters for type III, IV, and V secretion systems, and genes for putatively secreted molecules such as cholera-like toxins. The phylogenies indicate a recent transfer of seven genes in the virB gene cluster for a type IV secretion system from a catadapted B. henselae to a dog-adapted B. vinsonii strain. We show that the B. henselae GTA is functional and can transfer genes in vitro. We suggest that the maintenance of the GTA is driven by selection to increase the likelihood of horizontal gene transfer and argue that this process is beneficial at the population level, by facilitating adaptive evolution of the host-adaptation systems and thereby expansion of the host range size. The process counters gene loss and forces all cells to contribute to the production of the GTA and the secreted molecules. The results advance our understanding of the role that GTAs play for the evolution of bacterial genomes.
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| 13. |
- Guy, Lionel, et al.
(författare)
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A genome-wide study of recombination rate variation in Bartonella henselae
- 2012
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 12, s. 65-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Rates of recombination vary by three orders of magnitude in bacteria but the reasons for this variation is unclear. We performed a genome-wide study of recombination rate variation among genes in the intracellular bacterium Bartonella henselae, which has among the lowest estimated ratio of recombination relative to mutation in prokaryotes. Results: The 1.9 Mb genomes of B. henselae strains IC11, UGA10 and Houston-1 genomes showed only minor gene content variation. Nucleotide sequence divergence levels were less than 1% and the relative rate of recombination to mutation was estimated to 1.1 for the genome overall. Four to eight segments per genome presented significantly enhanced divergences, the most pronounced of which were the virB and trw gene clusters for type IV secretion systems that play essential roles in the infection process. Consistently, multiple recombination events were identified inside these gene clusters. High recombination frequencies were also observed for a gene putatively involved in iron metabolism. A phylogenetic study of this gene in 80 strains of Bartonella quintana, B. henselae and B. grahamii indicated different population structures for each species and revealed horizontal gene transfers across Bartonella species with different host preferences. Conclusions: Our analysis has shown little novel gene acquisition in B. henselae, indicative of a closed pan-genome, but higher recombination frequencies within the population than previously estimated. We propose that the dramatically increased fixation rate for recombination events at gene clusters for type IV secretion systems is driven by selection for sequence variability.
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| 14. |
- Guy, Lionel, et al.
(författare)
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Adaptive Mutations and Replacements of Virulence Traits in the Escherichia coli O104:H4 Outbreak Population
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5, s. e63027-
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Tidskriftsartikel (refereegranskat)abstract
- The sequencing of highly virulent Escherichia coli O104:H4 strains isolated during the outbreak of bloody diarrhea and hemolytic uremic syndrome in Europe in 2011 revealed a genome that contained a Shiga toxin encoding prophage and a plasmid encoding enteroaggregative fimbriae. Here, we present the draft genome sequence of a strain isolated in Sweden from a patient who had travelled to Tunisia in 2010 (E112/10) and was found to differ from the outbreak strains by only 38 SNPs in non-repetitive regions, 16 of which were mapped to the branch to the outbreak strain. We identified putatively adaptive mutations in genes for transporters, outer surface proteins and enzymes involved in the metabolism of carbohydrates. A comparative analysis with other historical strains showed that E112/10 contained Shiga toxin prophage genes of the same genotype as the outbreak strain, while these genes have been replaced by a different genotype in two otherwise very closely related strains isolated in the Republic of Georgia in 2009. We also present the genome sequences of two enteroaggregative E. coli strains affiliated with phylogroup A (C43/90 and C48/93) that contain the agg genes for the AAF/I-type fimbriae characteristic of the outbreak population. Interestingly, C43/90 also contained a tet/mer antibiotic resistance island that was nearly identical in sequence to that of the outbreak strain, while the corresponding island in the Georgian strains was most similar to E. coli strains of other serotypes. We conclude that the pan-genome of the outbreak population is shared with strains of the A phylogroup and that its evolutionary history is littered with gene replacement events, including most recently independent acquisitions of antibiotic resistance genes in the outbreak strains and its nearest neighbors. The results are summarized in a refined evolutionary model for the emergence of the O104:H4 outbreak population.
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| 15. |
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| 16. |
- Guy, Lionel, 1980-, et al.
(författare)
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genoPlotR : comparative gene and genome visualization in R
- 2010
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 26:18, s. 2334-2335
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Tidskriftsartikel (refereegranskat)abstract
- The amount of gene and genome data obtained by next-generation sequencing technologies generates a need for comparative visualization tools. Complementing existing software for comparison and exploration of genomics data, genoPlotR automatically creates publication-grade linear maps of gene and genomes, in a highly automatic, flexible and reproducible way. Availability: genoPlotR is a platform-independent R package, available with full source code under a GPL2 license at R-Forge: http://genoplotr.r-forge.r-project.org/ Contact: lionel.guy@ebc.uu.se
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| 17. |
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| 18. |
- Guy, Lionel, et al.
(författare)
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Low-coverage pyrosequencing reveals recombination and run-off replication in Bartonella henselae strains
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Bartonella henselae is a natural intracellular colonizer of cats, and is transferred by blood-sucking insect vectors. It is also an opportunistic human pathogen. Two strains of B. henselae, thought to be representative of the diversity of the species, were selected for low-coverage 454 sequencing. The comparison of these two strains to the published Houston-1 reveals very high nucleotide identity and low substitution and recombination, with the remarkable exception of phages and host-interaction genes such as type IV and V secretion systems. Among the few variable genes of unknown function, BH14680, an alpha-Proteobacteria-specific gene, shows faster evolution in Bartonella compared to other alpha-Proteobacteria. Its 5’ end, which is likely coding for a domain exposed extracellularly, is under positive or very relaxed selection, and might be involved in host-interaction processes. Finally, we show that a simple genome coverage analysis reveal major genomic events such as duplications and unusual replication modes, such as the run-off replication. The latter, combined with a gene transfer agent, is thought to be a novel way to increase substitution and recombination frequencies. An extensive analysis of all bacterial pyrosequencing projects showed that it is probably Bartonella-specific.
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| 19. |
- Guy, Lionel, 1980-
(författare)
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phyloSkeleton : taxon selection, data retrieval and marker identification for phylogenomics
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 33:8, s. 1230-1232
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Tidskriftsartikel (refereegranskat)abstract
- With the wealth of available genome sequences, a difficult and tedious part of inferring phylogenomic trees is now to select genomes with an appropriate taxon density in the different parts of the tree. The package described here offers tools to easily select the most representative organisms, following a set of simple rules based on taxonomy and assembly quality, to retrieve the genomes from public databases (NCBI, JGI), to annotate them if necessary, to identify given markers in these, and to prepare files for multiple sequence alignment.AVAILABILITY AND IMPLEMENTATION: phyloSkeleton is a Perl module and is freely available under GPLv3 at https://bitbucket.org/lionelguy/phyloskeleton/ CONTACT: lionel.guy@imbim.uu.se.
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| 20. |
- Guy, Lionel, et al.
(författare)
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The Archaeal Legacy of Eukaryotes : A Phylogenomic Perspective
- 2014
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Ingår i: Cold Spring Harbor Perspectives in Biology. - : Cold Spring Harbor Laboratory. - 1943-0264. ; 6:10, s. a016022-
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Tidskriftsartikel (refereegranskat)abstract
- The origin of the eukaryotic cell can be regarded as one of the hallmarks in the history of life on our planet. The apparent genomic chimerism in eukaryotic genomes is currently best explained by invoking a cellular fusion at the root of the eukaryotes that involves one archaeal and one or more bacterial components. Here, we use a phylogenomics approach to reevaluate the evolutionary affiliation between Archaea and eukaryotes, and provide further support for scenarios in which the nuclear lineage in eukaryotes emerged from within the archaeal radiation, displaying a strong phylogenetic affiliation with, or even within, the archaeal TACK superphylum. Further taxonomic sampling of archaeal genomes in this superphylum will certainly provide a better resolution in the events that have been instrumental for the emergence of the eukaryotic lineage.
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| 21. |
- Guy, Lionel, 1980-, et al.
(författare)
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The archaeal ‘TACK’ superphylum and the origin of eukaryotes
- 2011
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Ingår i: Trends in Microbiology. - : Elsevier BV. - 0966-842X .- 1878-4380. ; 19:12, s. 580-587
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Forskningsöversikt (refereegranskat)abstract
- Although most hypotheses to explain the emergence of the eukaryotic lineage are conflicting, some consensus exists concerning the requirement of a genomic fusion between archaeal and bacterial components. Recent phylogenomic studies have provided support for eocyte-like scenarios in which the alleged ‘archaeal parent’ of the eukaryotic cell emerged from the Crenarchaeota/Thaumarchaeota. Here, we provide evidence for a scenario in which this archaeal parent emerged from within the ‘TACK’ superphylum that comprises the Thaumarchaeota, Crenarchaeota and Korarchaeota, as well as the recently proposed phylum ‘Aigarchaeota’. In support of this view, functional and comparative genomics studies have unearthed an increasing number of features that are uniquely shared by the TACK superphylum and eukaryotes, including proteins involved in cytokinesis, membrane remodeling, cell shape determination and protein recycling.
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| 22. |
- Hudson, Lawrence N, et al.
(författare)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 23. |
- Hugoson, Eric, et al.
(författare)
-
Host Adaptation in Legionellales Is 1.9 Ga, Coincident with Eukaryogenesis
- 2022
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 39:3
-
Tidskriftsartikel (refereegranskat)abstract
- Bacteria adapting to living in a host cell caused the most salient events in the evolution of eukaryotes, namely the seminal fusion with an archaeon, and the emergence of both mitochondrion and chloroplast. A bacterial clade that may hold the key to understanding these events is the deep-branching gammaproteobacterial order Legionellales—containing among others Coxiella and Legionella—of which all known members grow inside eukaryotic cells. Here, by analyzing 35 novel Legionellales genomes mainly acquired through metagenomics, we show that this group is much more diverse than previously thought, and that key host-adaptation events took place very early in its evolution. Crucial virulence factors like the Type IVB secretion (Dot/Icm) system and two shared effector proteins were gained in the last Legionellales common ancestor (LLCA). Many metabolic gene families were lost in LLCA and its immediate descendants, including functions directly and indirectly related to molybdenum metabolism. On the other hand, genome sizes increased in the ancestors of the Legionella genus. We estimate that LLCA lived approximately 1.89 Ga, probably predating the last eukaryotic common ancestor by approximately 0.4–1.0 Gy. These elements strongly indicate that host adaptation arose only once in Legionellales, and that these bacteria were using advanced molecular machinery to exploit and manipulate host cells early in eukaryogenesis.
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| 24. |
- Hugoson, Eric, et al.
(författare)
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miComplete : weighted quality evaluation of assembled microbial genomes
- 2020
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 36:3, s. 936-937
-
Tidskriftsartikel (refereegranskat)abstract
- SUMMARY: Metagenomics and single-cell genomics have revolutionized the study of microorganisms, increasing our knowledge of microbial genomic diversity by orders of magnitude. A major issue pertaining to metagenome-assembled genomes (MAGs) and single-cell amplified genomes (SAGs) is to estimate their completeness and redundancy. Most approaches rely on counting conserved gene markers. In miComplete, we introduce a weighting strategy, where we normalize the presence/absence of markers by their median distance to the next marker in a set of complete reference genomes. This approach alleviates biases introduced by the presence/absence of shorter DNA pieces containing many markers, e.g. ribosomal protein operons.AVAILABILITY AND IMPLEMENTATION: miComplete is written in Python 3 and released under GPLv3. Source code and documentation are available at https://bitbucket.org/evolegiolab/micomplete.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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| 25. |
- Hurtig, Fredrik, 1988-
(författare)
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Divisive structures : Two billions years of biofilament evolution
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Our understanding of the functional and regulatory complexity that existed in the eukaryotic progenitor is poor, and investigations have been hindered by our nebulous understanding of where eukaryotes stem from. Recently discovered archaeal lineages with hitherto unseen homology to eukaryotic systems suggest archaea can further our understanding of the eukaryotic cell’s ancestry. However, much of archaeal biology remains largely unexplored. Two eukaryotic systems with archaeal homologues, namely the actin and ESCRT-III protein filament systems, are essential for diverse processes in eukaryotic biology. In this thesis, we show that an archaeal homologue of ESCRT-III divides the cell under proteasomal regulation, a regulatory mechanism central to eukaryotic cell cycle regulation. Additionally, we show how predicted putative profilin and gelsolin homologues regulate the postulated proto-cytoskeleton of Asgard archaea. In investigating the function and regulation of these archaeal systems we demonstrate compelling parallels between archaeal and eukaryotic regulatory strategies which stresses the close evolutionary relationship that exists between these two domains.
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| 26. |
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| 27. |
- Hägglund, Emil, et al.
(författare)
-
TADA : Taxonomy-Aware Dataset Aggregator
- 2023
-
Ingår i: Bioinformatics. - : Oxford University Press. - 1367-4803 .- 1367-4811. ; 39:12
-
Tidskriftsartikel (refereegranskat)abstract
- The profusion of sequenced genomes across the bacterial and archeal domains offers unprecedented possibilities for phylogenetic and comparative genomic analyses. In general, phylogenetic reconstruction is improved by the use of more data. However, including all available data is (i) not computationally tractable, and (ii) prone to biases, as the abundance of genomes is very unequally distributed over the biological diversity. Thus, in most cases, subsampling taxa to build a phylogeny is necessary. Currently, though, there is no available software to perform that handily. Here we present TADA, a taxonomic-aware dataset selection workflow that allows sampling across user-defined portions of the prokaryotic diversity with variable granularity, while setting constraints on genome quality and balance between branches.
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| 28. |
- Kacar, Betul, et al.
(författare)
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Resurrecting ancestral genes in bacteria to interpret ancient biosignatures
- 2017
-
Ingår i: Philosophical Transactions. Series A. - : The Royal Society. - 1364-503X .- 1471-2962. ; 375:2109
-
Tidskriftsartikel (refereegranskat)abstract
- Two datasets, the geologic record and the genetic content of extant organisms, provide complementary insights into the history of how key molecular components have shaped or driven global environmental and macroevolutionary trends. Changes in global physico-chemical modes over time are thought to be a consistent feature of this relationship between Earth and life, as life is thought to have been optimizing protein functions for the entirety of its approximately 3.8 billion years of history on the Earth. Organismal survival depends on how well critical genetic and metabolic components can adapt to their environments, reflecting an ability to optimize efficiently to changing conditions. The geologic record provides an array of biologically independent indicators of macroscale atmospheric and oceanic composition, but provides little in the way of the exact behaviour of the molecular components that influenced the compositions of these reservoirs. By reconstructing sequences of proteins that might have been present in ancient organisms, we can downselect to a subset of possible sequences that may have been optimized to these ancient environmental conditions. How can one use modern life to reconstruct ancestral behaviours? Configurations of ancient sequences can be inferred from the diversity of extant sequences, and then resurrected in the laboratory to ascertain their biochemical attributes. One way to augment sequence-based, single-gene methods to obtain a richer and more reliable picture of the deep past, is to resurrect inferred ancestral protein sequences in living organisms, where their phenotypes can be exposed in a complex molecular-systems context, and then to link consequences of those phenotypes to biosignatures that were preserved in the independent historical repository of the geological record. As a first step beyond single-molecule reconstruction to the study of functional molecular systems, we present here the ancestral sequence reconstruction of the beta-carbonic anhydrase protein. We assess how carbonic anhydrase proteins meet our selection criteria for reconstructing ancient biosignatures in the laboratory, which we term palaeophenotype reconstruction.This article is part of the themed issue 'Reconceptualizing the origins of life'.
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| 29. |
- Karlsson, Philip A., et al.
(författare)
-
Molecular Characterization of Multidrug-Resistant Yersinia enterocolitica From Foodborne Outbreaks in Sweden
- 2021
-
Ingår i: Frontiers in Microbiology. - : Frontiers Media S.A.. - 1664-302X. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- The foodborne pathogen Yersinia enterocolitica causes gastrointestinal infections worldwide. In the spring of 2019, the Swedish Public Health Agency and Statens Serum Institut in Denmark independently identified an outbreak caused by Yersinia enterocolitica 4/O:3 that after sequence comparison turned out to be a cross-border outbreak. A trace-back investigation suggested shipments of fresh prewashed spinach from Italy as a common source for the outbreak. Here, we determined the genome sequences of five Y. enterocolitica clinical isolates during the Swedish outbreak using a combination of Illumina HiSeq short-read and Nanopore Technologies’ MinION long-read whole-genome sequencing. WGS results showed that all clinical strains have a fully assembled chromosome of approximately 4.6 Mbp in size and a 72-kbp virulence plasmid; one of the strains was carrying an additional 5.7-kbp plasmid, pYE-tet. All strains showed a high pathogen probability score (87.5%) with associated genes for virulence, all of which are closely related to an earlier clinical strain Y11 from Germany. In addition, we identified a chromosomally encoded multidrug-resistance cassette carrying resistance genes against chloramphenicol (catA1), streptomycin (aadA1), sulfonamides (sul1), and a mercury resistance module. This chromosomally encoded Tn2670 transposon has previously been reported associated with IncFII plasmids in Enterobacteriaceae: a Shigella flexneri clinical isolate from Japan in 1950s, a Klebsiella pneumoniae outbreak from Australia in 1997, and Salmonella enterica serovar Typhimurium. Interestingly, we identified an additional 5.7-kbp plasmid with tetB (encoding an ABC transporter), Rep, and its own ORI and ORIt sites, sharing high homology with small tetB-Rep plasmids from Pasteurellaceae. This is the first time that Tn2670 and Pasteurellaceae plasmids have been reported in Y. enterocolitica. Taken together, our study showed that the Swedish Y. enterocolitica outbreak strains acquired multi-antibiotic and metal-resistance genes through horizontal gene transfer, suggesting a potential reservoir of intraspecies dissemination of multidrug-resistance genes among foodborne pathogens. This study also highlights the concern of food-chain contamination of prewashed vegetables as a perpetual hazard against public health.
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| 30. |
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| 31. |
- Kämpfer, Peter, et al.
(författare)
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Proposal of Coetzeea brasiliensis gen. nov. sp. nov. isolated from larvae of Anopheles darlingi
- 2016
-
Ingår i: International Journal of Systematic and Evolutionary Microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 66, s. 5211-5217
-
Tidskriftsartikel (refereegranskat)abstract
- A Gram-stain-negative, rod-shaped strain, Braz8T, isolated from larvae ofAnopheles darlingiwas investigatedusing a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that strainBraz8Twas related most closely to species of the genusThorsellia, with 95.6, 96.5 and 96.6% similarity to thetype strains ofThorsellia anophelis,Thorsellia kandunguensisandThorsellia kenyensis, respectively, andformed a separate branch in the phylogenetic tree next to the monophyletic cluster of the genusThorsellia.Chemotaxonomic data supported the allocation of the strain to the familyThorselliaceae. The major fatty acidswere C18:1!7c, C16:0and C14:0. The quinone system was composed of ubiquinones Q-8 and Q-7 (1:0.3),the predominant polar lipids were diphosphatidylglycerol and phosphatidylglycerol, and the polyamine patternshowed the major compound putrescine. However, qualitative and quantitative differences in the majorpolyamine, polar lipid profile and fatty acid patterns distinguished strain Braz8Tfrom species of the genusThorsellia. Phylogenetic analysis based on 16S rRNA gene sequences, average nucleotide identity, DNA–DNAhybridization, multilocus sequence analysis as well as physiological and biochemical tests distinguished strainBraz8Tboth genotypically and phenotypically from the threeThorselliaspecies but also showed its placementin the familyThorselliaceae. Thus, strain Braz8Tis considered to represent a novel species of a new genus mostclosely related to the genusThorsellia, for which the nameCoetzeea brasiliensisgen. nov., sp. nov. is proposed.The type strain ofCoetzeea brasiliensisis Braz8T(=LMG 29552T=CIP 111088T)
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| 32. |
- Kämpfer, Peter, et al.
(författare)
-
Proposal of Thorsellia kenyensis sp. nov. and Thorsellia kandunguensis sp. nov., isolated from the larvae of Anopheles arabiensis as members of the family Thorselliaceae fam. nov.
- 2015
-
Ingår i: International Journal of Systematic and Evolutionary Microbiology. - : Microbiology Society. - 1466-5026 .- 1466-5034. ; 65, s. 444-451
-
Tidskriftsartikel (refereegranskat)abstract
- Two Gram-negative, rod-shaped strains, T2.1T and W5.1.1T, isolated from larvae of the mosquito Anopheles arabiensis, were investigated using a polyphasic approach. On the basis of 16S rRNA gene sequence similarity studies, strains T2.1T and W5.1.1T were shown to belong to the genus Thorsellia, both showing 97.8 % similarity to the type strain of Thorsellia anophelis, with 98.1 % similarity to each other. Chemotaxonomic data supported the allocation of the strains to the genus Thorsellia: their major fatty acids were C18 : 1ω7c, C16 : 0 and C14 : 0 and they harboured a ubiquinone Q-8 quinone system and a polyamine pattern with the major compound 1,3-diaminopropane. Qualitative and quantitative differences in their polar lipid profiles distinguished strains T2.1T and W5.1.1T from each other and from T. anophelis. Average nucleotide identity (ANI), DNA–DNA hybridization, multilocus sequence analysis (MLSA) as well as physiological and biochemical tests allowed T2.1T and W5.1.1T to be distinguished both genotypically and phenotypically from each other and from the type strain of T. anophelis. Thus, we propose that these isolates represent two novel species of the genus Thorsellia, named Thorsellia kenyensis sp. nov. (type strain T2.1T = CCM 8545T = LMG 28483T = CIP 110829T) and Thorsellia kandunguensis sp. nov. (type strain W5.1.1T = LMG 28213T = CIP 110794T). Furthermore, phylogenetic analysis based on nearly full-length 16S rRNA gene sequences showed that the genus Thorsellia forms a separate branch, distinct from the families Enterobacteriaceae, Pasteurellaceae and Orbaceae. As a consequence, a new family Thorselliaceae fam. nov. is proposed. An emended description of Thorsellia anophelis is also provided.
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| 33. |
- Leenheer, Daniël, et al.
(författare)
-
Rapid adaptations of Legionella pneumophila to the human host
- 2023
-
Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 9:3
-
Tidskriftsartikel (refereegranskat)abstract
- Legionella pneumophila are host-adapted bacteria that infect and reproduce primarily in amoeboid protists. Using similar infection mechanisms, they infect human macrophages, and cause Legionnaires’ disease, an atypical pneumonia, and the milder Pontiac fever. We hypothesized that, despite the similarities in infection mechanisms, the hosts are different enough that there exist high-selective value mutations that would dramatically increase the fitness of Legionella inside the human host. By comparing a large number of isolates from independent infections, we identified two genes, mutated in three unrelated patients, despite the short duration of the incubation period (2–14 days). One is a gene coding for an outer membrane protein (OMP) belonging to the OmpP1/FadL family. The other is a gene coding for an EAL-domain-containing protein involved in cyclic-di-GMP regulation, which in turn modulates flagellar activity. The clinical strain, carrying the mutated EAL-domain-containing homologue, grows faster in macrophages than the wild-type strain, and thus appears to be better adapted to the human host. As human-to-human transmission is very rare, fixation of these mutations into the population and spread into the environment is unlikely. Therefore, parallel evolution – here mutations in the same genes observed in independent human infections – could point to adaptations to the accidental human host. These results suggest that despite the ability of L. pneumophila to infect, replicate in and exit from macrophages, its human-specific adaptations are unlikely to be fixed in the population.
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| 34. |
- Leenheer, Daniël, et al.
(författare)
-
Rapid, in-patient adaptations of Legionella pneumophila to the human host
- 2024
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Legionella pneumophila are host-adapted bacteria that infect and reproduce primarily in amoeboid protists. Using similar infection mechanisms, they infect human macrophages, and cause Legionnaires’ disease, an atypical pneumonia, and the milder Pontiac fever. We hypothesized that, despite these similarities, the hosts are different enough so that there exist high-selective value mutations that would dramatically increase the fitness of Legionella inside the human host. By comparing a large number of isolates from independent infections, we identified two genes, mutated in three unrelated patients, despite the short duration of the incubation period (2-14 days). One is a gene coding for an outer membrane protein (OMP) belonging to the OmpP1/FadL family. The clinical strain, carrying the mutated OMP homolog, grows faster in macrophages than the wild type strain, and thus appears to be better adapted to the human host. The other is a gene coding for a protein involved in cyclic-di-GMP regulation, which in turn modulates flagellar activity. As human-to-human transmission is very rare, fixation of these mutations into the population and spread into the environment is unlikely. Therefore, convergent evolution – here mutations in the same genes observed in independent human infections – could point to adaptations to the accidental human host. These results suggest that despite its ability to infect, replicate, and disperse from amoebae, L. pneumophila is not well adapted to the human host.
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| 35. |
- Lind, Anders E., et al.
(författare)
-
Genomes of two archaeal endosymbionts show convergent adaptations to an intracellular lifestyle.
- 2018
-
Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 12:11, s. 2655-2667
-
Tidskriftsartikel (refereegranskat)abstract
- Endosymbiosis is a widespread phenomenon in the microbial world and can be based on diverse interactions between endosymbiont and host cell. The vast majority of the known endosymbiotic interactions involve bacteria that have invaded eukaryotic host cells. However, methanogenic archaea have been found to thrive in anaerobic, hydrogenosome-containing protists and it was suggested that this symbiosis is based on the transfer of hydrogen. Here, we used culture-independent genomics approaches to sequence the genomes of two distantly related methanogenic endosymbionts that have been acquired in two independent events by closely related anaerobic ciliate hosts Nyctotherus ovalis and Metopus contortus, respectively. The sequences obtained were then validated as originating from the ciliate endosymbionts by in situ probing experiments. Comparative analyses of these genomes and their closest free-living counterparts reveal that the genomes of both endosymbionts are in an early stage of adaptation towards endosymbiosis as evidenced by the large number of genes undergoing pseudogenization. For instance, the observed loss of genes involved in amino acid biosynthesis in both endosymbiont genomes indicates that the endosymbionts rely on their hosts for obtaining several essential nutrients. Furthermore, the endosymbionts appear to have gained significant amounts of genes of potentially secreted proteins, providing targets for future studies aiming to elucidate possible mechanisms underpinning host-interactions. Altogether, our results provide the first genomic insights into prokaryotic endosymbioses from the archaeal domain of life.
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| 36. |
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| 37. |
- Lundin, Erik, et al.
(författare)
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Experimental Determination and Prediction of the Fitness Effects of Random Point Mutations in the Biosynthetic Enzyme HisA
- 2018
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 35:3, s. 704-718
-
Tidskriftsartikel (refereegranskat)abstract
- The distribution of fitness effects of mutations is a factor of fundamental importance in evolutionary biology. We determined the distribution of fitness effects of 510 mutants that each carried between 1 and 10 mutations (synonymous and nonsynonymous) in the hisA gene, encoding an essential enzyme in the L-histidine biosynthesis pathway of Salmonella enterica. For the full set of mutants, the distribution was bimodal with many apparently neutral mutations and many lethal mutations. For a subset of 81 single, nonsynonymous mutants most mutations appeared neutral at high expression levels, whereas at low expression levels only a few mutations were neutral. Furthermore, we examined how the magnitude of the observed fitness effects was correlated to several measures of biophysical properties and phylogenetic conservation.We conclude that for HisA: (i) The effect of mutations can be masked by high expression levels, such that mutations that are deleterious to the function of the protein can still be neutral with regard to organism fitness if the protein is expressed at a sufficiently high level; (ii) the shape of the fitness distribution is dependent on the extent to which the protein is rate-limiting for growth; (iii) negative epistatic interactions, on an average, amplified the combined effect of nonsynonymous mutations; and (iv) no single sequence-based predictor could confidently predict the fitness effects of mutations in HisA, but a combination of multiple predictors could predict the effect with a SD of 0.04 resulting in 80% of the mutations predicted within 12% of their observed selection coefficients.
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| 38. |
- Mahajan, Mayank, et al.
(författare)
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Paralogization and New Protein Architectures in Planctomycetes Bacteria with Complex Cell Structures
- 2020
-
Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 37:4, s. 1020-1040
-
Tidskriftsartikel (refereegranskat)abstract
- Bacteria of the phylum Planctomycetes have a unique cell plan with an elaborate intracellular membrane system, thereby resembling eukaryotic cells. The origin and evolution of these remarkable features is debated. To study the evolutionary genomics of bacteria with complex cell architectures, we have re-sequenced the 9.2 Mb genome of the model organism Gemmata obscuriglobus and sequenced the 10 Mb genome of Gemmata massiliana Soil9, the 7.9 Mb genome of Cjuql4 and the 6.7 Mb genome of Tuwongella immobilis, all of which belong to the family Gemmataceae. A gene flux analysis of the Planctomycetes revealed a massive emergence of novel protein families at multiple nodes within the Gemmataceae. The expanded protein families have unique multi-domain architectures composed of domains that are characteristic of prokaryotes, such as the sigma factor domain of extracytoplasmic sigma factors, and domains that have proliferated in eukaryotes, such as the WD40, LRR, TPR and Ser/Thr kinase domains. Proteins with identifiable domains in the Gemmataceae have longer lengths and linkers than proteins in most other bacteria, and the analyses suggest that these traits were ancestrally present in the Planctomycetales. A broad comparison of protein length distribution profiles revealed an overlap between the longest proteins in prokaryotes and the shortest proteins in eukaryotes. We conclude that the many similarities between proteins in the Planctomycetales and the eukaryotes are due to convergent evolution and that there is no strict boundary between prokaryotes and eukaryotes with regard to features such as gene paralogy, protein length and protein domain composition patterns.
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| 39. |
- Martijn, Joran, et al.
(författare)
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Deep mitochondrial origin outside the sampled alphaproteobacteria
- 2018
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 557:7703, s. 101-105
-
Tidskriftsartikel (refereegranskat)abstract
- Mitochondria are ATP-generating organelles, the endosymbiotic origin of which was a key event in the evolution of eukaryotic cells(1). Despite strong phylogenetic evidence that mitochondria had an alphaproteobacterial ancestry(2), efforts to pinpoint their closest relatives among sampled alphaproteobacteria have generated conflicting results, complicating detailed inferences about the identity and nature of the mitochondrial ancestor. While most studies support the idea that mitochondria evolved from an ancestor related to Rickettsiales(3-9), an order that includes several host-associated pathogenic and endosymbiotic lineages(10,11), others have suggested that mitochondria evolved from a free-living group(12-14). Here we re-evaluate the phylogenetic placement of mitochondria. We used genome-resolved binning of oceanic metagenome datasets and increased the genomic sampling of Alphaproteobacteria with twelve divergent clades, and one clade representing a sister group to all Alphaproteobacteria. Subsequent phylogenomic analyses that specifically address long branch attraction and compositional bias artefacts suggest that mitochondria did not evolve from Rickettsiales or any other currently recognized alphaproteobacterial lineage. Rather, our analyses indicate that mitochondria evolved from a proteobacterial lineage that branched off before the divergence of all sampled alphaproteobacteria. In light of this new result, previous hypotheses on the nature of the mitochondrial ancestor(6,15,16) should be re-evaluated.
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| 40. |
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| 41. |
- Martijn, Joran, et al.
(författare)
-
Single-cell genomics of a rare environmental alphaproteobacterium provides unique insights into Rickettsiaceae evolution
- 2015
-
Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 9:11, s. 2373-2385
-
Tidskriftsartikel (refereegranskat)abstract
- The bacterial family Rickettsiaceae includes a group of well-known etiological agents of many human and vertebrate diseases, including epidemic typhus-causing pathogen Rickettsia prowazekii. Owing to their medical relevance, rickettsiae have attracted a great deal of attention and their host-pathogen interactions have been thoroughly investigated. All known members display obligate intracellular lifestyles, and the best-studied genera, Rickettsia and Orientia, include species that are hosted by terrestrial arthropods. Their obligate intracellular lifestyle and host adaptation is reflected in the small size of their genomes, a general feature shared with all other families of the Rickettsiales. Yet, despite that the Rickettsiaceae and other Rickettsiales families have been extensively studied for decades, many details of the origin and evolution of their obligate host-association remain elusive. Here we report the discovery and single-cell sequencing of 'Candidatus Arcanobacter lacustris', a rare environmental alphaproteobacterium that was sampled from Damariscotta Lake that represents a deeply rooting sister lineage of the Rickettsiaceae. Intriguingly, phylogenomic and comparative analysis of the partial 'Candidatus Arcanobacter lacustris' genome revealed the presence chemotaxis genes and vertically inherited flagellar genes, a novelty in sequenced Rickettsiaceae, as well as several host-associated features. This finding suggests that the ancestor of the Rickettsiaceae might have had a facultative intracellular lifestyle. Our study underlines the efficacy of single-cell genomics for studying microbial diversity and evolution in general, and for rare microbial cells in particular.
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| 42. |
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| 43. |
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| 44. |
- Neuvonen, Minna M., et al.
(författare)
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The genome of Rhizobiales bacteria in predatory ants reveals urease gene functions but no genes for nitrogen fixation
- 2016
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Gut-associated microbiota of ants include Rhizobiales bacteria with affiliation to the genus Bartonella. These bacteria may enable the ants to fix atmospheric nitrogen, but no genomes have been sequenced yet to test the hypothesis. Sequence reads from a member of the Rhizobiales were identified in the data collected in a genome project of the ant Harpegnathos saltator. We present an analysis of the closed 1.86 Mb genome of the ant-associated bacterium, for which we suggest the species name Candidatus Tokpelaia hoelldoblerii. A phylogenetic analysis reveals a relationship to Bartonella and Brucella, which infect mammals. Novel gene acquisitions include a gene for a putative extracellular protein of more than 6,000 amino acids secreted by the type I secretion system, which may be involved in attachment to the gut epithelium. No genes for nitrogen fixation could be identified, but genes for a multi-subunit urease protein complex are present in the genome. The urease genes are also present in Brucella, which has a fecal-oral transmission pathway, but not in Bartonella, which use blood-borne transmission pathways. We hypothesize that the gain and loss of the urease function is related to transmission strategies and lifestyle changes in the host-associated members of the Rhizobiales.
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| 45. |
- Nystedt, Björn, 1978-, et al.
(författare)
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Evolution of Host Adaptation Systems in the Mammalian Blood Specialist Bartonella
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Bacteria of the genus Bartonella are facultative intracellular bacteria infecting the red blood cells of mammals. Bartonella isolates have now been reported from a wide range of mammalian host species, including humans, domestic animals such as pets and livestock, as well as many wild animals such as deer, moose, kangaroo, and whales. Here, we present the first major genus-wide investigation of host-adaptation systems in Bartonella, using 5 published and 5 draft genome sequences. The sampling includes both clinical and natural isolates, and represent well the major phylogenetic diversity of the genus. Our study reveals four distinct protein families of Type V Secretion Systems (T5SS) shared by all sequenced members of the genus. We also show that a recently identified gene transfer agent (GTA) consisting of a defective phage is, surprisingly, the most conserved gene cluster among all Bartonella-specific or imported genes, strongly emphasizing the functional importance of this system for the life-style and evolution of Bartonella.
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| 46. |
- Odelgard, Anna, et al.
(författare)
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Phylogeny and Expansion of Serine/Threonine Kinases in Phagocytotic Bacteria in the Phylum Planctomycetota
- 2024
-
Ingår i: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The recently isolated bacterium "Candidatus Uabimicrobium amorphum" is the only known prokaryote that can engulf other bacterial cells. Its proteome contains a high fraction of proteins involved in signal transduction systems, which is a feature normally associated with multicellularity in eukaryotes. Here, we present a protein-based phylogeny which shows that "Ca. Uabimicrobium amorphum" represents an early diverging lineage that clusters with the Saltatorellus clade within the phylum Planctomycetota. A gene flux analysis indicated a gain of 126 protein families for signal transduction functions in "Ca. Uabimicrobium amorphum", of which 66 families contained eukaryotic-like Serine/Threonine kinases with Pkinase domains. In total, we predicted 525 functional Serine/Threonine kinases in "Ca. Uabimicrobium amorphum", which represent 8% of the proteome and is the highest fraction of Serine/Threonine kinases in a bacterial proteome. The majority of Serine/Threonine kinases in this species are membrane proteins and 30% contain long, tandem arrays of WD40 or TPR domains. The pKinase domain was predicted to be located in the cytoplasm, while the WD40 and TPR domains were predicted to be located in the periplasm. Such domain combinations were also identified in the Serine/Threonine kinases of other species in the Planctomycetota, although in much lower abundances. A phylogenetic analysis of the Serine/Threonine kinases in the Planctomycetota inferred from the Pkinase domain alone provided support for lineage-specific expansions of the Serine/Threonine kinases in "Ca. Uabimicrobium amorphum". The results imply that expansions of eukaryotic-like signal transduction systems are not restricted to multicellular organisms, but have occurred in parallel in prokaryotes with predatory lifestyles and phagocytotic-like behaviors.
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| 47. |
- Panchaud, Alexandre, et al.
(författare)
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M-protein and other intrinsic virulence factors of Streptococcus pyogenes are encoded on an ancient pathogenicity island
- 2009
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 10:198
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Tidskriftsartikel (refereegranskat)abstract
- Background The increasing number of completely sequenced bacterial genomes allows comparing their architecture and genetic makeup. Such new information highlights the crucial role of lateral genetic exchanges in bacterial evolution and speciation. Results Here we analyzed the twelve sequenced genomes of Streptococcus pyogenes by a naïve approach that examines the preferential nucleotide usage along the chromosome, namely the usage of G versus C (GC-skew) and T versus A (TA-skew). The cumulative GC-skew plot presented an inverted V-shape composed of two symmetrical linear segments, where the minimum and maximum corresponded to the origin and terminus of DNA replication. In contrast, the cumulative TA-skew presented a V-shape, which segments were interrupted by several steep slopes regions (SSRs), indicative of a different nucleotide composition bias. Each S. pyogenes genome contained up to nine individual SSRs, encompassing all described strain-specific prophages. In addition, each genome contained a similar unique non-phage SSR, the core of which consisted of 31 highly homologous genes. This core includes the M-protein, other mga-related factors and other virulence genes, totaling ten intrinsic virulence genes. In addition to a high content in virulence-related genes and to a peculiar nucleotide bias, this SSR, which is 47 kb-long in a M1GAS strain, harbors direct repeats and a tRNA gene, suggesting a mobile element. Moreover, its complete absence in a M-protein negative group A Streptococcus natural isolate demonstrates that it could be spontaneously lost, but in vitro deletion experiments indicates that its excision occurred at very low rate. The stability of this SSR, combined to its presence in all sequenced S. pyogenes sequenced genome, suggests that it results from an ancient acquisition. Conclusion Thus, this non-phagic SSR is compatible with a pathogenicity island, acquired before S. pyogenes speciation. Its potential excision might bear relevance for vaccine development, because vaccines targeting M-protein might select for M-protein-negative variants that still carry other virulence determinants.
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| 48. |
- Rosseel, Liesbeth, et al.
(författare)
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Contemporary European practice in transcatheter aortic valve implantation: results from the 2022 European TAVI Pathway Registry.
- 2023
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Ingår i: Frontiers in cardiovascular medicine. - 2297-055X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- A steep rise in the use of transcatheter aortic valve implantation (TAVI) for the management of symptomatic severe aortic stenosis occurred. Minimalist TAVI procedures and streamlined patient pathways within experienced Heart Valve Centres are designed to overcome the challenges of ever-increasing procedural volume.The 2022 European TAVI Pathway Survey aims to describe contemporary TAVI practice across Europe.Between October and December 2022, TAVI operators from 32 European countries were invited to complete an online questionnaire regarding their current practice.Responses were available from 147 TAVI centres in 26 countries. In 2021, the participating centres performed a total number of 27,223 TAVI procedures, with a mean of 185 TAVI cases per centre (median 138; IQR 77-194). Treatment strategies are usually (87%) discussed at a dedicated Heart Team meeting. Transfemoral TAVI is performed with local anaesthesia only (33%), with associated conscious sedation (60%), or under general anaesthesia (7%). Primary vascular access is percutaneous transfemoral (99%) with secondary radial access (52%). After uncomplicated TAVI, patients are transferred to a high-, medium-, or low-care unit in 28%, 52%, and 20% of cases, respectively. Time to discharge is day 1 (12%), day 2 (31%), day 3 (29%), or day 4 or more (28%).Reported adoption of minimalist TAVI techniques is common among European TAVI centres, but rates of next-day discharge remain low. This survey highlights the significant progress made in refining TAVI treatment and pathways in recent years and identifies possible areas for further improvement.
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| 49. |
- Saw, Jimmy H., et al.
(författare)
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Exploring microbial dark matter to resolve the deep archaeal ancestry of eukaryotes
- 2015
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Ingår i: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 370:1678
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Tidskriftsartikel (refereegranskat)abstract
- The origin of eukaryotes represents an enigmatic puzzle, which is still lacking a number of essential pieces. Whereas it is currently accepted that the process of eukaryogenesis involved an interplay between a host cell and an alphaproteo-bacterial endosymbiont, we currently lack detailed information regarding the identity and nature of these players. A number of studies have provided increasing support for the emergence of the eukaryotic host cell from within the archaeal domain of life, displaying a specific affiliation with the archaeal TACK superphylum. Recent studies have shown that genomic exploration of yet-uncultivated archaea, the so-called archaeal 'dark matter', is able to provide unprecedented insights into the process of eukaryogenesis. Here, we provide an overview of state-of-the-art cultivation-independent approaches, and demonstrate how these methods were used to obtain draft genome sequences of several novel members of the TACK superphylum, including Lokiarchaeum, two representatives of the Miscellaneous Crenarchaeotal Group (Bathyarchaeota), and a Korarchaeum-related lineage. The maturation of cultivation-independent genomics approaches, as well as future developments in next-generation sequencing technologies, will revolutionize our current view of microbial evolution and diversity, and provide profound new insights into the early evolution of life, including the enigmatic origin of the eukaryotic cell.
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| 50. |
- Sentchilo, Vladimir, et al.
(författare)
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Community-wide plasmid gene mobilization and selection
- 2013
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Ingår i: The ISME Journal. - : Springer Science and Business Media LLC. - 1751-7362 .- 1751-7370. ; 7:6, s. 1173-1186
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Tidskriftsartikel (refereegranskat)abstract
- Plasmids have long been recognized as an important driver of DNA exchange and genetic innovation in prokaryotes. The success of plasmids has been attributed to their independent replication from the host's chromosome and their frequent self-transfer. It is thought that plasmids accumulate, rearrange and distribute nonessential genes, which may provide an advantage for host proliferation under selective conditions. In order to test this hypothesis independently of biases from culture selection, we study the plasmid metagenome from microbial communities in two activated sludge systems, one of which receives mostly household and the other chemical industry wastewater. We find that plasmids from activated sludge microbial communities carry among the largest proportion of unknown gene pools so far detected in metagenomic DNA, confirming their presumed role of DNA innovators. At a system level both plasmid metagenomes were dominated by functions associated with replication and transposition, and contained a wide variety of antibiotic and heavy metal resistances. Plasmid families were very different in the two metagenomes and grouped in deep-branching new families compared with known plasmid replicons. A number of abundant plasmid replicons could be completely assembled directly from the metagenome, providing insight in plasmid composition without culturing bias. Functionally, the two metagenomes strongly differed in several ways, including a greater abundance of genes for carbohydrate metabolism in the industrial and of general defense factors in the household activated sludge plasmid metagenome. This suggests that plasmids not only contribute to the adaptation of single individual prokaryotic species, but of the prokaryotic community as a whole under local selective conditions.
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