| 1. |
- Rojas, Danny, et al.
(författare)
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Bats (Chiroptera:Noctilionoidea) Challenge a Recent Origin of Extant Neotropical Diversity
- 2016
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Ingår i: Systematic Biology. - : Oxford University Press (OUP). - 1063-5157 .- 1076-836X. ; 65:3, s. 432-448
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms underlying the high extant biodiversity in the Neotropics have been controversial since the 19th century. Support for the influence of period-specific changes on diversification often rests on detecting more speciation events during a particular period. The timing of speciation events may reflect the influence of incomplete taxon sampling, protracted speciation, and null processes of lineage accumulation. Here we assess the influence of these factors on the timing of speciation with new multilocus data for New World noctilionoid bats (Chiroptera: Noctilionoidea). Biogeographic analyses revealed the importance of the Neotropics in noctilionoid diversification, and the critical role of dispersal. We detected no shift in speciation rate associated with the Quaternary or pre-Quaternary periods, and instead found an increase in speciation linked to the evolution of the subfamily Stenodermatinae (similar to 18 Ma). Simulations modeling constant speciation and extinction rates for the phylogeny systematically showed more speciation events in the Quaternary. Since recording more divergence events in the Quaternary can result from lineage accumulation, the age of extant sister species cannot be interpreted as supporting higher speciation rates during this period. Instead, analyzing the factors that influence speciation requires modeling lineage-specific traits and environmental, spatial, and ecological drivers of speciation.
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| 2. |
- Tavares, Valeria da C., et al.
(författare)
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Out of the Antilles : Fossil phylogenies support reverse colonization of bats to South America
- 2018
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Ingår i: Journal of Biogeography. - : John Wiley & Sons. - 0305-0270 .- 1365-2699. ; 45:4, s. 859-873
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Previous phylogenies of extant short-faced bats (Chiroptera: Stenodermatina) supported either two colonization events from the mainland to the Antilles, or reverse colonization, but lacked both fossil data and statistical modelling of biogeography. Recent multi-locus phylogenies of noctilionoid bats and likelihood modelling of ancestral ranges support a continental origin for the clade. We include all known extinct and extant stenodermatina species and apply statistical modelling to test competing biogeographical hypotheses. Location: The Neotropics, including the Antilles. Methods: We combined mitochondrial and nuclear sequences with 302 new morphological characters to infer phylogenies. Bayesian tip-dating analyses applied codon models to protein-coding genes, with relaxed molecular clocks fitting a compound Poisson process. The combined maximum clade credibility tree was used in comparisons of alternative biogeographical models. Results: The new phylogenies support the fossil Cubanycteris silvai as sister to all extant species of short-faced bats. Among Artibeus (the sister group to short-faced bats), the Antillean fossil A. anthonyi has distinctive characters and is nested within the subgenus Artibeus. The common ancestor of all short-faced bats is inferred to be Antillean, as a mainland origin is unlikely. Founder-event speciation is the most probable process explaining the distribution of these highly divergent fossil lineages. Main conclusions: Dated, character-based phylogenies of fossil species are indispensable for biogeographical inference: without fossils, biogeographical analyses find a mainland origin for short-faced bats. The rate of founder speciation in this clade is twice as high as the estimate from noctilionoids in general, highlighting the role of founder events in the diversification of island taxa. Although rare, reverse colonization contributes key species to continental communities. Short-faced bats, including Cubanycteris, share biomechanical adaptations for a strong bite conferring access to harder figs. We hypothesize these adaptations and characters related to roosting ecology enabled ancestral lineages to successfully establish and diversify on the mainland.
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| 3. |
- Warsi, Omar M., et al.
(författare)
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Staphylococcus aureus mutants resistant to the feed-additive monensin show increased virulence and altered purine metabolism
- 2024
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Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Ionophores are antibacterial compounds that affect bacterial growth by changing intracellular concentrations of the essential cations, sodium and potassium. They are extensively used in animal husbandry to increase productivity and reduce infectious diseases, but our understanding of the potential for and effects of resistance development to ionophores is poorly known. Thus, given their widespread global usage, it is important to determine the potential negative consequences of ionophore use on human and animal health. In this study, we demonstrate that exposure to the ionophore monensin can select for resistant mutants in the human and animal pathogen Staphylococcus aureus, with a majority of the resistant mutants showing increased growth rates in vitro and/or in mice. Whole-genome sequencing and proteomic analysis of the resistant mutants show that the resistance phenotype is associated with de-repression of de novo purine synthesis, which could be achieved through mutations in different transcriptional regulators including mutations in the gene purR, the repressor of the purine de novo synthesis pathway. This study shows that mutants with reduced susceptibility to the ionophore monensin can be readily selected and highlights an unexplored link between ionophore resistance, purine metabolism, and fitness in pathogenic bacteria.IMPORTANCEThis study demonstrates a novel link between ionophore resistance, purine metabolism, and virulence/fitness in the key human and animal pathogen Staphylococcus aureus. The results show that mutants with reduced susceptibility to the commonly used ionophore monensin can be readily selected and that the reduced susceptibility observed is associated with an increased expression of the de novo purine synthesis pathway. This study increases our understanding of the impact of the use of animal feed additives on both human and veterinary medicine.
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| 4. |
- Guo, Xiaohu, et al.
(författare)
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Structure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme family
- 2021
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The first S-adenosyl methionine (SAM) degrading enzyme (SAMase) was discovered in bacteriophage T3, as a counter-defense against the bacterial restriction-modification system, and annotated as a SAM hydrolase forming 5’-methyl-thioadenosine (MTA) and L-homoserine. From environmental phages, we recently discovered three SAMases with barely detectable sequence similarity to T3 SAMase and without homology to proteins of known structure. Here, we present the very first phage SAMase structures, in complex with a substrate analogue and the product MTA. The structure shows a trimer of alpha–beta sandwiches similar to the GlnB-like superfamily, with active sites formed at the trimer interfaces. Quantum-mechanical calculations, thin-layer chromatography, and nuclear magnetic resonance spectroscopy demonstrate that this family of enzymes are not hydrolases but lyases forming MTA and L-homoserine lactone in a unimolecular reaction mechanism. Sequence analysis and in vitro and in vivo mutagenesis support that T3 SAMase belongs to the same structural family and utilizes the same reaction mechanism.
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| 5. |
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| 6. |
- Pereira, Catia, et al.
(författare)
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Pervasive Selection for Clinically Relevant Resistance and Media Adaptive Mutations at Very Low Antibiotic Concentrations
- 2023
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Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 40:1
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Tidskriftsartikel (refereegranskat)abstract
- Experimental evolution studies have shown that weak antibiotic selective pressures (i.e., when the antibiotic concentrations are far below the minimum inhibitory concentration, MIC) can select resistant mutants, raising several unanswered questions. First, what are the lowest antibiotic concentrations at which selection for de novo resistance mutations can occur? Second, with weak antibiotic selections, which other types of adaptive mutations unrelated to the antibiotic selective pressure are concurrently enriched? Third, are the mutations selected under laboratory settings at subMIC also observed in clinical isolates? We addressed these questions using Escherichia coli populations evolving at subMICs in the presence of either of four clinically used antibiotics: fosfomycin, nitrofurantoin, tetracycline, and ciprofloxacin. Antibiotic resistance evolution was investigated at concentrations ranging from 1/4th to 1/2000th of the MIC of the susceptible strain (MICsusceptible). Our results show that evolution was rapid across all the antibiotics tested, and selection for fosfomycin- and nitrofurantoin-resistant mutants was observed at a concentration as low as 1/2000th of MICsusceptible. Several of the evolved resistant mutants showed increased growth yield and exponential growth rates, and outcompeted the susceptible ancestral strain in the absence of antibiotics as well, suggesting that adaptation to the growth environment occurred in parallel with the selection for resistance. Genomic analysis of the resistant mutants showed that several of the mutations selected under these conditions are also found in clinical isolates, demonstrating that experimental evolution at very low antibiotic levels can help in identifying novel mutations that contribute to bacterial adaptation during subMIC exposure in real-life settings.
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| 7. |
- Pinheiro, Fernanda, et al.
(författare)
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Metabolic fitness landscapes predict the evolution of antibiotic resistance
- 2021
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 5:5, s. 677-687
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Tidskriftsartikel (refereegranskat)abstract
- This study develops metabolic fitness models that integrate drug action with evolutionary response to predict growth rates of resistance mutations and prevalent mechanisms of antibiotic resistance in Escherichia coli. Bacteria evolve resistance to antibiotics by a multitude of mechanisms. A central, yet unsolved question is how resistance evolution affects cell growth at different drug levels. Here, we develop a fitness model that predicts growth rates of common resistance mutants from their effects on cell metabolism. The model maps metabolic effects of resistance mutations in drug-free environments and under drug challenge; the resulting fitness trade-off defines a Pareto surface of resistance evolution. We predict evolutionary trajectories of growth rates and resistance levels, which characterize Pareto resistance mutations emerging at different drug dosages. We also predict the prevalent resistance mechanism depending on drug and nutrient levels: low-dosage drug defence is mounted by regulation, evolution of distinct metabolic sectors sets in at successive threshold dosages. Evolutionary resistance mechanisms include membrane permeability changes and drug target mutations. These predictions are confirmed by empirical growth inhibition curves and genomic data of Escherichia coli populations. Our results show that resistance evolution, by coupling major metabolic pathways, is strongly intertwined with systems biology and ecology of microbial populations.
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| 8. |
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| 9. |
- Warsi, Omar M., et al.
(författare)
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Different adaptive strategies in E-coli populations evolving under macronutrient limitation and metal ion limitation
- 2018
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Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adaptive responses to nutrient limitation involve mutations that increase the efficiency of usage or uptake of the limiting nutrient. However, starvation of different nutrients has contrasting effects on physiology, resulting in different evolutionary responses. Most studies performed to understand these evolutionary responses have focused only on macronutrient limitation. Hence our understanding of adaptation under limitation of other forms of nutrients is limited. In this study, we compared the evolutionary response in populations evolving under growth-limiting conditions for a macronutrient and a major cation. Results: We evolved eight populations of E. coli in nutrient-limited chemostats for 400 generations to identify the genetic basis of the mechanisms involved in efficient usage of two nutrients: nitrogen and magnesium. Our population genomic sequencing work, based on this study and previous work, allowed us to identify targets of selection under these nutrient limiting conditions. Global transcriptional regulators glnGL were targets of selection under nitrogen starvation, while proteins involved in outer-membrane biogenesis (genes from the lpt operon) were targets of selection under magnesium starvation. The protein involved in cell-cycle arrest (yhaV) was a target of selection in both environments. We re-constructed specific mutants to analyze the effect of individual mutations on fitness in nutrient limiting conditions in chemostats and in batch cultures. We further demonstrated that adaptation to nitrogen starvation proceeds via a nutrient specific mechanism, while that to magnesium starvation involves a more general mechanism. Conclusions: Our results show two different forms of adaptive strategies under limitation of nutrients that effect cellular physiology in different ways. Adaptation to nitrogen starvation proceeds by upregulation of transcriptional regulator glnG and subsequently of transporter protein amtB, both of which results in increased nitrogen scavenging ability of the cell. On the other hand, adaptation to magnesium starvation proceeds via the restructuring of the cell outer-membrane, allowing magnesium to be redistributed to other biological processes. Also, adaptation to the chemostat environment involves selection for loss of function mutations in genes that under nutrient-limiting conditions interfere with continuous growth.
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| 10. |
- Warsi, Omar M., et al.
(författare)
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Evolutionary implications of Liebig's law of the minimum : Selection under low concentrations of two nonsubstitutable nutrients
- 2017
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 7:14, s. 5296-5309
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between different axes of an organism's niche determine the evolutionary trajectory of a population. An extreme case of these interactions is predicted from ecological theory in Liebig's law of the minimum. This law states that in environments where multiple nutrients are in relatively low concentrations, only one nutrient will affect the growth of the organism. This implies that the evolutionary response of the population would be dictated by the most growth-limiting nutrient. Alternatively, it is possible that an initial adaptation to the most limiting nutrient results in other nutrients present in low concentration affecting the evolutionary dynamics of the population. To test these hypotheses, we conducted twelve evolution experiments in chemostats using Escherichia coli populations: four under nitrogen limitation, four under magnesium limitation, and four in which both nitrogen and magnesium are in low concentrations. In the last environment, only magnesium seems to limit growth (Low Nitrogen Magnesium Limited environment, LNML). We observe a decrease in nitrogen concentration in the LNML environment over the course of our evolution experiment indicating that nitrogen might become limiting in these environments. Genetic reconstruction results show that clones adapted to magnesium limitation have genes involved in nitrogen starvation, that is, glnG (nitrogen starvation transcriptional regulator) and amtB (transport protein) to be upregulated only in the LNML environment as compared to magnesium-limiting environments. Together, our results highlights that in low-nutrient environments, adaptation to the growth-limiting nutrient results in other nutrients at low concentrations to play a role in the evolutionary dynamics of the population.
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| 11. |
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| 12. |
- Warsi, Omar M., et al.
(författare)
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Selection for novel metabolic capabilities in Salmonella enterica
- 2019
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Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 73:5, s. 990-1000
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Tidskriftsartikel (refereegranskat)abstract
- Bacteria are known to display extensive metabolic diversity and many studies have shown that they can use an extensive repertoire of small molecules as carbon‐ and energy sources. However, it is less clear to what extent a bacterium can expand its existing metabolic capabilities by acquiring mutations that, for example, rewire its metabolic pathways. To investigate this capability and potential for evolution of novel phenotypes, we sampled large populations of mutagenized Salmonella enterica to select very rare mutants that can grow on minimal media containing 124 low molecular weight compounds as sole carbon sources. We found mutants growing on 18 of these novel carbon sources, and identified the causal mutations that allowed growth for four of them. Mutations that relieve physiological constraints or increase expression of existing pathways were found to be important contributors to the novel phenotypes. For the remaining 14 novel phenotypes, whole genome sequencing of independent mutants and genetic analysis suggested that these novel metabolic phenotypes result from a combination of multiple mutations. This work, by virtue of identifying the genetic and mechanistic basis for new metabolic capabilities, sheds light on the properties of adaptive landscapes underlying the evolution of novel phenotypes.
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| 13. |
- Warsi, Omar M., et al.
(författare)
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Vesicle-enriched secretomes alter bacterial competitive abilities and are drivers of evolution in microbial communities
- 2023
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Ingår i: FEMS Microbiology Ecology. - : Oxford University Press. - 0168-6496 .- 1574-6941. ; 99:12
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Tidskriftsartikel (refereegranskat)abstract
- Microbial membrane vesicles can carry compounds that inhibit bacterial growth, but how they impact the fitness of the vesicle-producing bacterial species and influence community dynamics remain unexplored questions. To address these questions, we examined the effect of vesicle-enriched secretomes (VESs) in different single-species and multi-species systems. Effects of VESs on single-species growth dynamics were determined for nine bacterial species belonging to four genera (Escherichia, Salmonella, Pseudomonas and Bacillus) in nutrient-rich and poor growth media. Results showed both species-specific and nutrient-dependent effects of the VESs on bacterial growth. The strongest antagonistic effects were observed for VES isolated from the natural isolates of E. coli, while those isolated from P. aeruginosa PA14 affected the highest number of species. We further demonstrated that these VESs altered the competitive abilities of the species involved in two-species (S. Typhimurium LT2 and S. arizonae) and three-species systems (E. coli, S. Typhimurium LT2 and B. subtilis). Finally, using experimental evolution we showed that different bacterial species could rapidly acquire mutations that abrogated the antagonistic effects of VESs. This study demonstrates how VESs can contribute in shaping microbial communities, both by increasing the competitive ability of a given bacterial species and as a driver of genetic adaptation.
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