scholarly journals Resident microbial communities inhibit growth and antibiotic-resistance evolution of Escherichia coli in human gut microbiome samples

PLoS Biology ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. e3000465 ◽  
Author(s):  
Michael Baumgartner ◽  
Florian Bayer ◽  
Katia R. Pfrunder-Cardozo ◽  
Angus Buckling ◽  
Alex R. Hall
2019 ◽  
Author(s):  
Michael Baumgartner ◽  
Florian Bayer ◽  
Katia R. Pfrunder-Cardozo ◽  
Angus Buckling ◽  
Alex R. Hall

AbstractCountering the rise of antibiotic resistant pathogens requires improved understanding of how resistance emerges and spreads in individual species, which are often embedded in complex microbial communities such as the human gut microbiome. Interactions with other microorganisms in such communities might suppress growth and resistance evolution of individual species (e.g. via resource competition), but could also potentially accelerate resistance evolution via horizontal transfer of resistance genes. It remains unclear how these different effects balance out, partly because it is difficult to observe them directly. Here, we used a gut microcosm approach to quantify the effect of three human gut microbiome communities on growth and resistance evolution of a focal strain of Escherichia coli. We found the resident microbial communities not only suppressed growth and colonization by focal E. coli, they also prevented it from evolving antibiotic resistance upon exposure to a beta-lactam antibiotic. With samples from all three human donors, our focal E. coli strain only evolved antibiotic resistance in the absence of the resident microbial community, even though we found resistance genes, including a highly effective resistance plasmid, in resident microbial communities. We identified physical constraints on plasmid transfer that can explain why our focal strain failed to acquire some of these beneficial resistance genes, and we found some chromosomal resistance mutations were only beneficial in the absence of the resident microbiota. This suggests, depending on in situ gene transfer dynamics, interactions with resident microbiota can inhibit antibiotic resistance evolution of individual species.


2020 ◽  
Vol 53 ◽  
pp. 35-43 ◽  
Author(s):  
Ross S McInnes ◽  
Gregory E McCallum ◽  
Lisa E Lamberte ◽  
Willem van Schaik

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bruno G. N. Andrade ◽  
Tobias Goris ◽  
Haithem Afli ◽  
Felipe H. Coutinho ◽  
Alberto M. R. Dávila ◽  
...  

Abstract Background The high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin, caused by mobilized colistin resistance (mcr) genes, poses an unprecedented threat to human health. Understanding the spread, evolution, and distribution of such genes among human populations will help in the development of strategies to diminish their occurrence. To tackle this problem, we investigated the distribution and prevalence of potential mcr genes in the human gut microbiome using a set of bioinformatics tools to screen the Unified Human Gastrointestinal Genome (UHGG) collection for the presence, synteny and phylogeny of putative mcr genes, and co-located antibiotic resistance genes. Results A total of 2079 antibiotic resistance genes (ARGs) were classified as mcr genes in 2046 metagenome assembled genomes (MAGs), distributed across 1596 individuals from 41 countries, of which 215 were identified in plasmidial contigs. The genera that presented the largest number of mcr-like genes were Suterella and Parasuterella. Other potential pathogens carrying mcr genes belonged to the genus Vibrio, Escherichia and Campylobacter. Finally, we identified a total of 22,746 ARGs belonging to 21 different classes in the same 2046 MAGs, suggesting multi-resistance potential in the corresponding bacterial strains, increasing the concern of ARGs impact in the clinical settings. Conclusion This study uncovers the diversity of mcr-like genes in the human gut microbiome. We demonstrated the cosmopolitan distribution of these genes in individuals worldwide and the co-presence of other antibiotic resistance genes, including Extended-spectrum Beta-Lactamases (ESBL). Also, we described mcr-like genes fused to a PAP2-like domain in S. wadsworthensis. These novel sequences increase our knowledge about the diversity and evolution of mcr-like genes. Future research should focus on activity, genetic mobility and a potential colistin resistance in the corresponding strains to experimentally validate those findings.


2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Wei Yan ◽  
A. Brantley Hall ◽  
Xiaofang Jiang

AbstractAntibiotic-resistance genes (ARGs) regulated by invertible promoters can mitigate the fitness cost of maintaining ARGs in the absence of antibiotics and could potentially prolong the persistence of ARGs in bacterial populations. However, the origin, prevalence, and distribution of these ARGs regulated by invertible promoters remains poorly understood. Here, we sought to assess the threat posed by ARGs regulated by invertible promoters by systematically searching for ARGs regulated by invertible promoters in the human gut microbiome and examining their origin, prevalence, and distribution. Through metagenomic assembly of 2227 human gut metagenomes and genomic analysis of the Unified Human Gastrointestinal Genome (UHGG) collection, we identified ARGs regulated by invertible promoters and categorized them into three classes based on the invertase-regulating phase variation. In the human gut microbiome, ARGs regulated by invertible promoters are exclusively found in Bacteroidales species. Through genomic analysis, we observed that ARGs regulated by invertible promoters have convergently originated from ARG insertions into glycan-synthesis loci that were regulated by invertible promoters at least three times. Moreover, all three classes of invertible promoters regulating ARGs are located within integrative conjugative elements (ICEs). Therefore, horizontal transfer via ICEs could explain the wide taxonomic distribution of ARGs regulated by invertible promoters. Overall, these findings reveal that glycan-synthesis loci regulated by invertible promoters in Bacteroidales species are an important hotspot for the emergence of clinically-relevant ARGs regulated by invertible promoters.


2020 ◽  
Author(s):  
Wenshan Zheng ◽  
Shijie Zhao ◽  
Yehang Yin ◽  
Huidan Zhang ◽  
David M. Needham ◽  
...  

AbstractWe present Microbe-seq, a high-throughput single-microbe method that yields strain-resolved genomes from complex microbial communities. We encapsulate individual microbes into droplets with microfluidics and liberate their DNA, which we amplify, tag with droplet-specific barcodes, and sequence. We use Microbe-seq to explore the human gut microbiome; we collect stool samples from a single individual, sequence over 20,000 microbes, and reconstruct nearly-complete genomes of almost 100 bacterial species, including several with multiple subspecies strains. We use these genomes to probe genomic signatures of microbial interactions: we reconstruct the horizontal gene transfer (HGT) network within the individual and observe far greater exchange within the same bacterial phylum than between different phyla. We probe bacteria-virus interactions; unexpectedly, we identify a significant in vivo association between crAssphage, an abundant bacteriophage, and a single strain of Bacteroides vulgatus. Microbe-seq contributes high-throughput culture-free capabilities to investigate genomic blueprints of complex microbial communities with single-microbe resolution.


2021 ◽  
Author(s):  
Wei Yan ◽  
A. Brantley Hall ◽  
Xiangfang Jiang

ABSTRACTPhase-variable antibiotic resistance genes (ARGs) can mitigate the fitness cost of maintaining ARGs in the absence of antibiotics and could potentially prolong the persistence of ARGs in bacterial populations. However, the origin, prevalence, and distribution of phase-variable ARGs remains poorly understood. Here, we sought to assess the threat posed by phase-variable ARGs by systematically searching for phase-variable ARGs in the human gut microbiome and examining their origin, prevalence, and distribution. Through metagenomic assembly of 2227 human gut metagenomes and genomic analysis of the Unified Human Gastrointestinal Genome (UHGG) collection, we identified phase-variable ARGs and categorized them into three classes based on the invertase regulating phase variation. In the human gut microbiome, phase-variable ARGs are commonly and exclusively distributed in Bacteroidales species. Through genomic analysis, we observed that phase-variable ARGs have convergently originated from ARG insertions into phase-variable capsule polysaccharide biosynthesis (CPS) loci at least three times. Moreover, all identified phase-variable ARGs are located within integrative conjugative elements (ICEs). Therefore, horizontal transfer via ICEs could explain the wide taxonomic distribution of phase-variable ARGs. Overall, these findings reveal that phase-variable CPS loci in Bacteroidales species are an important hotspot for the emergence of clinically-relevant phase-variable ARGs.


2020 ◽  
Author(s):  
Ryan L. Clark ◽  
Bryce M. Connors ◽  
David M. Stevenson ◽  
Susan E. Hromada ◽  
Joshua J. Hamilton ◽  
...  

ABSTRACTThe assembly of microbial communities and functions emerge from a complex and dynamic web of interactions. A major challenge in microbiome engineering is identifying organism configurations with community-level behaviors that achieve a desired function. The number of possible subcommunities scales exponentially with the number of species in a system, creating a vast experimental design space that is challenging to even sparsely traverse. We develop a model-guided experimental design framework for microbial communities and apply this method to explore the functional landscape of the health-relevant metabolite butyrate using a 25-member synthetic human gut microbiome community. Based on limited experimental measurements, our model accurately forecasts community assembly and butyrate production at every possible level of complexity. Our results elucidate key ecological and molecular mechanisms driving butyrate production including inter-species interactions, pH and hydrogen sulfide. Our model-guided iterative approach provides a flexible framework for understanding and predicting community functions for a broad range of applications.


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