| 1. |
- Brandt, Christian, et al.
(författare)
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Assessing genetic diversity and similarity of 435 KPC-carrying plasmids
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The global spread and diversification of multidrug-resistant Gram-negative (MRGN) bacteria poses major challenges to healthcare. In particular, carbapenem-resistant Klebsiella pneumoniae strains have been frequently identified in infections and hospital-wide outbreaks. The most frequently underlying resistance gene (bla(KPC)) has been spreading over the last decade in the health care setting. bla(KPC) seems to have rapidly diversified and has been found in various species and on different plasmid types. To review the progress and dynamics of this diversification, all currently available KPC plasmids in the NCBI database were analysed in this work. Plasmids were grouped into 257 different representative KPC plasmids, of which 79.4% could be clearly assigned to incompatibility (Inc) group or groups. In almost half of all representative plasmids, the KPC gene is located on Tn4401 variants, emphasizing the importance of this transposon type for the transmission of KPC genes to other plasmids. The transposons also seem to be responsible for the occurrence of altered or uncommon fused plasmid types probably due to incomplete transposition. Moreover, many KPC plasmids contain genes that encode proteins promoting recombinant processes and mutagenesis; in consequence accelerating the diversification of KPC genes and other colocalized resistance genes.
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| 2. |
- Burkhard, Benjamin, et al.
(författare)
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Mapping and assessing ecosystem services in the EU - Lessons learned from the ESMERALDA approach of integration
- 2018
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Ingår i: One Ecosystem. - : Pensoft Publishers. - 2367-8194. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The European Union (EU) Horizon 2020 Coordination and Support Action ESMERALDA aimed at developing guidance and a flexible methodology for Mapping and Assessment of Ecosystems and their Services (MAES) to support the EU member states in the implementation of the EU Biodiversity Strategy’s Target 2 Action 5. ESMERALDA’s key tasks included network creation, stakeholder engagement, enhancing ecosystem services mapping and assessment methods across various spatial scales and value domains, work in case studies and support of EU member states in MAES implementation. Thus ESMERALDA aimed at integrating various project outcomes around four major strands: i) Networking, ii) Policy, iii) Research and iv) Application. The objective was to provide guidance for integrated ecosystem service mapping and assessment that can be used for sustainable decision-making in policy, business, society, practice and science at EU, national and regional levels. This article presents the overall ESMERALDA approach of integrating the above-mentioned project components and outcomes and provides an overview of how the enhanced methods were applied and how they can be used to support MAES implementation in the EU member states. Experiences with implementing such a large pan-European Coordination and Support Action in the context of EU policy are discussed and recommendations for future actions are given.
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| 3. |
- Colleoni, Marco, et al.
(författare)
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Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.
- 2018
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Ingår i: The Lancet. Oncology. - : Elsevier. - 1474-5488 .- 1470-2045. ; 19:1, s. 127-138
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Tidskriftsartikel (refereegranskat)abstract
- In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women.We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing.Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85·8% (95% CI 84·2-87·2) in the intermittent letrozole group compared with 87·5% (86·0-88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93-1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group).In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them.Novartis and the International Breast Cancer Study Group.
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| 4. |
- Danielsson, Rebecca, et al.
(författare)
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Methane Production in Dairy Cows Correlates with Rumen Methanogenic and Bacterial Community Structure
- 2017
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Methane (CH4) is produced as an end product from feed fermentation in the rumen. Yield of CH4 varies between individuals despite identical feeding conditions. To get a better understanding of factors behind the individual variation, 73 dairy cows given the same feed but differing in CH4 emissions were investigated with focus on fiber digestion, fermentation end products and bacterial and archaeal composition. In total 21 cows (12 Holstein, 9 Swedish Red) identified as persistent low, medium or high CH4 emitters over a 3 month period were furthermore chosen for analysis of microbial community structure in rumen fluid. This was assessed by sequencing the V4 region of 16S rRNA gene and by quantitative qPCR of targeted Methanobrevibacter groups. The results showed a positive correlation between low CH4 emitters and higher abundance of Methanobrevibacter ruminantium clade. Principal coordinate analysis (PCoA) on operational taxonomic unit (OTU) level of bacteria showed two distinct clusters (P < 0.01) that were related to CH4 production. One cluster was associated with low CH4 production (referred to as cluster L) whereas the other cluster was associated with high CH4 production (cluster H) and the medium emitters occurred in both clusters. The differences between clusters were primarily linked to differential abundances of certain OTUs belonging to Prevotella. Moreover, several OTUs belonging to the family Succinivibrionaceae were dominant in samples belonging to cluster L. Fermentation pattern of volatile fatty acids showed that proportion of propionate was higher in cluster L, while proportion of butyrate was higher in cluster H. No difference was found in milk production or organic matter digestibility between cows. Cows in cluster L had lower CH4/kg energy corrected milk (ECM) compared to cows in cluster H, 8.3 compared to 9.7 g CH4/kg ECM, showing that low CH4 cows utilized the feed more efficient for milk production which might indicate a more efficient microbial population or host genetic differences that is reflected in bacterial and archaeal (or methanogens) populations.
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| 5. |
- Fabiana, Paula, et al.
(författare)
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The potential for polyphosphate metabolism in Archaea and anaerobic polyphosphate formation in Methanosarcina mazei
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Inorganic polyphosphate (polyP) is ubiquitous across all forms of life, but the study of its metabolism has been mainly confined to bacteria and yeasts. Few reports detail the presence and accumulation of polyP in Archaea, and little information is available on its functions and regulation. Here, we report that homologs of bacterial polyP metabolism proteins are present across the major taxa in the Archaea, suggesting that archaeal populations may have a greater contribution to global phosphorus cycling than has previously been recognised. We also demonstrate that polyP accumulation can be induced under strictly anaerobic conditions, in response to changes in phosphate (Pi) availability, i.e. Pi starvation, followed by incubation in Pi replete media (overplus), in cells of the methanogenic archaeon Methanosarcina mazei. Pi-starved M. mazei cells increased transcript abundance of the alkaline phosphatase (phoA) gene and of the high-affinity phosphate transport (pstSCAB-phoU) operon: no increase in polyphosphate kinase 1 (ppk1) transcript abundance was observed. Subsequent incubation of Pi-starved M. mazei cells under Pi replete conditions, led to a 237% increase in intracellular polyphosphate content and a > 5.7-fold increase in ppk1 gene transcripts. Ppk1 expression in M. mazei thus appears not to be under classical phosphate starvation control.
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| 6. |
- Liu, Tong, et al.
(författare)
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Importance of inoculum source and initial community structure for biogas production from agricultural substrates
- 2017
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Ingår i: Bioresource Technology. - : Elsevier BV. - 0960-8524 .- 1873-2976. ; 245, s. 768-777
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the importance of inoculum source for start-up and operation of biogas processes. Three different inocula with different community structure were used to initiate six laboratory continuous stirred tank reactor (CSTR) processes operated with a grass manure mixture as substrate. The processes were evaluated by chemical and microbiological analysis, by targeting the overall bacterial community and potential cellulose-degrading bacteria. As expected, the results showed a large difference in community structure in the inocula and in process performance during the first hydraulic retention time (HRT). However, the performance and overall microbial community structure became similar in the reactors over time. An inoculum from a high-ammonia process, characterized by low diversity and low degradation efficiency, took the longest time to reach stability and final methane yield. The overall bacterial community was mainly shaped by the operating conditions but, interestingly, potential cellulose-degrading bacteria seemed mainly to originate from the substrate.
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| 7. |
- Manzoor, Shahid, et al.
(författare)
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Complete genome sequence of Methanoculleus bourgensis strain MAB1, the syntrophic partner of mesophilic acetate-oxidising bacteria (SAOB)
- 2016
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Ingår i: Standards in Genomic Sciences. - : Springer Science and Business Media LLC. - 1944-3277. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Methanoculleus bourgensis strain MAB1 has been identified as the hydrogenotrophic partner of mesophilic acetate-oxidising bacteria, a syntrophic relationship operating close to the thermodynamic equilibrium and of considerable importance in ammonia-rich engineered biogas processes. Methanoculleus bourgensis strain MAB1 belongs to the order Methanomicrobiales, family Methanomicrobiaceae, within the phylum Euryarchaeota. The genome shows a total size of 2,859,299 bp encoding 3450 predicted protein-encoding genes, of which only 1472 (43 %) have been assigned tentative functions. The genome encodes further 44 tRNA genes and three rRNA genes (5S, 16S and 23S rRNA). This study presents assembling and annotation features as well as genomic traits related to ammonia tolerance and methanogenesis.
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| 8. |
- Manzoor, Shahid, et al.
(författare)
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Genome-Guided Analysis and Whole Transcriptome Profiling of the Mesophilic Syntrophic Acetate Oxidising Bacterium Syntrophaceticus schinkii
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Syntrophaceticus schinkii is a mesophilic, anaerobic bacterium capable of oxidising acetate to CO2 and H-2 in intimate association with a methanogenic partner, a syntrophic relationship which operates close to the energetic limits of microbial life. Syntrophaceticus schinkii has been identified as a key organism in engineered methane-producing processes relying on syntrophic acetate oxidation as the main methane-producing pathway. However, due to strict cultivation requirements and difficulties in reconstituting the thermodynamically unfavourable acetate oxidation, the physiology of this functional group is poorly understood. Genome-guided and whole transcriptome analyses performed in the present study provide new insights into habitat adaptation, syntrophic acetate oxidation and energy conservation. The working draft genome of Syntrophaceticus schinkii indicates limited metabolic capacities, with lack of organic nutrient uptake systems, chemotactic machineries, carbon catabolite repression and incomplete biosynthesis pathways. Ech hydrogenase, [ FeFe] hydrogenases, [ NiFe] hydrogenases, F1F0-ATP synthase and membrane-bound and cytoplasmic formate dehydrogenases were found clearly expressed, whereas Rnf and a predicted oxidoreductase/heterodisulphide reductase complex, both found encoded in the genome, were not expressed under syntrophic growth condition. A transporter sharing similarities to the high-affinity acetate transporters of aceticlastic methanogens was also found expressed, suggesting that Syntrophaceticus schinkii can potentially compete with methanogens for acetate. Acetate oxidation seems to proceed via the Wood-Ljungdahl pathway as all genes involved in this pathway were highly expressed. This study shows that Syntrophaceticus schinkii is a highly specialised, habitat-adapted organism relying on syntrophic acetate oxidation rather than metabolic versatility. By expanding its complement of respiratory complexes, it might overcome limiting bioenergetic barriers, and drive efficient energy conservation from reactions operating close to the thermodynamic equilibrium, which might enable S. schinkii to occupy the same niche as the aceticlastic methanogens. The knowledge gained here will help specify process conditions supporting efficient and robust biogas production and will help identify mechanisms important for the syntrophic lifestyle.
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| 9. |
- Manzoor, Shahid, et al.
(författare)
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Genome-Guided Analysis of Clostridium ultunense and Comparative Genomics Reveal Different Strategies for Acetate Oxidation and Energy Conservation in Syntrophic Acetate-Oxidising Bacteria
- 2018
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Syntrophic acetate oxidation operates close to the thermodynamic equilibrium and very little is known about the participating organisms and their metabolism. Clostridium ultunense is one of the most abundant syntrophic acetate-oxidising bacteria (SAOB) that are found in engineered biogas processes operating with high ammonia concentrations. It has been proven to oxidise acetate in cooperation with hydrogenotrophic methanogens. There is evidence that the Wood-Ljungdahl (WL) pathway plays an important role in acetate oxidation. In this study, we analysed the physiological and metabolic capacities of C. ultunense strain Esp and strain BST on genome scale and conducted a comparative study of all the known characterised SAOB, namely Syntrophaceticus schinkii, Thermacetogenium phaeum, Tepidanaerobacter acetatoxydans, and Pseudothermotoga lettingae. The results clearly indicated physiological robustness to be beneficial for anaerobic digestion environments and revealed unexpected metabolic diversity with respect to acetate oxidation and energy conservation systems. Unlike S. schinkii and Th. phaeum, C. ultunense clearly does not employ the oxidative WL pathway for acetate oxidation, as its genome (and that of P. lettingae) lack important key genes. In both of those species, a proton motive force is likely formed by chemical protons involving putative electron-bifurcating [Fe-Fe] hydrogenases rather than proton pumps. No genes encoding a respiratory Ech (energy-converting hydrogenase), as involved in energy conservation in Th. phaeum and S. schinkii, were identified in C. ultunense and P. lettingae. Moreover, two respiratory complexes sharing similarities to the proton-translocating ferredoxin: NAD(+) oxidoreductase (Rnf) and the Na+ pumping NADH: quinone hydrogenase (NQR) were predicted. These might form a respiratory chain that is involved in the reduction of electron acceptors rather than protons. However, involvement of these complexes in acetate oxidation in C. ultunense and P. lettingae needs further study. This genome-based comparison provides a solid platform for future meta-proteomics and meta-transcriptomics studies and for metabolic engineering, control, and monitoring of SAOB.
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| 10. |
- Manzoor, Shahid, et al.
(författare)
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Working draft genome sequence of the mesophilic acetate oxidizing bacterium Syntrophaceticus schinkii strain Sp3
- 2015
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Ingår i: Standards in Genomic Sciences. - : Springer Science and Business Media LLC. - 1944-3277. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Syntrophaceticus schinkii strain Sp3 is a mesophilic syntrophic acetate oxidizing bacterium, belonging to the Clostridia class within the phylum Firmicutes, originally isolated from a mesophilic methanogenic digester. It has been shown to oxidize acetate in co-cultivation with hydrogenotrophic methanogens forming methane. The draft genome shows a total size of 3,196,921 bp, encoding 3,688 open reading frames, which includes 3,445 predicted protein-encoding genes and 55 RNA genes. Here, we are presenting assembly and annotation features as well as basic genomic properties of the type strain Sp3.
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