scholarly journals Bacteroidales species in the human gut are a reservoir of antibiotic resistance genes regulated by invertible promoters

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Wei Yan ◽  
A. Brantley Hall ◽  
Xiaofang Jiang
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Phase Variation ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Human Gut ◽  
Bacterial Populations ◽  
Human Gut Microbiome ◽  
Metagenomic Assembly

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.

scholarly journals Bacteroidales species are a reservoir of phase-variable antibiotic resistance genes in the human gut microbiome

2021 ◽  
Author(s):  
Wei Yan ◽  
A. Brantley Hall ◽  
Xiangfang Jiang
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Phase Variation ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Phase Variable ◽  
Human Gut ◽  
Polysaccharide Biosynthesis ◽  
Human Gut Microbiome

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.

scholarly journals Horizontal transfer of antibiotic resistance genes in the human gut microbiome

2020 ◽  
Vol 53 ◽  
pp. 35-43 ◽  
Author(s):  
Ross S McInnes ◽  
Gregory E McCallum ◽  
Lisa E Lamberte ◽  
Willem van Schaik
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Horizontal Transfer ◽  
Antibiotic Resistance Genes ◽  
Human Gut ◽  
Human Gut Microbiome

scholarly journals Putative mobilized colistin resistance genes in the human gut microbiome

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bruno G. N. Andrade ◽  
Tobias Goris ◽  
Haithem Afli ◽  
Felipe H. Coutinho ◽  
Alberto M. R. Dávila ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Genes ◽  
Future Research ◽  
Human Populations ◽  
Bacterial Strains ◽  
Colistin Resistance ◽  
Human Gut ◽  
Human Gut Microbiome

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.

scholarly journals Phylogenetic barriers to horizontal transfer of antimicrobial peptide resistance genes in the human gut microbiota

2018 ◽  
Author(s):  
Bálint Kintses ◽  
Orsolya Méhi ◽  
Eszter Ari ◽  
Mónika Számel ◽  
Ádám Györkei ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Gut Microbiota ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Horizontal Transfer ◽  
Bacterial Species ◽  
Antibiotic Resistance Genes ◽  
Genetic Exchange ◽  
Human Gut ◽  
Human Gut Microbiota

AbstractThe human gut microbiota has adapted to the presence of antimicrobial peptides (AMPs) that are ancient components of immune defence. Despite important medical relevance, it has remained unclear whether AMP resistance genes in the gut microbiome are available for genetic exchange between bacterial species. Here we show that AMP- and antibiotic-resistance genes differ in their mobilization patterns and functional compatibilities with new bacterial hosts. First, whereas AMP resistance genes are widespread in the gut microbiome, their rate of horizontal transfer is lower than that of antibiotic resistance genes. Second, gut microbiota culturing and functional metagenomics revealed that AMP resistance genes originating from phylogenetically distant bacteria only have a limited potential to confer resistance inEscherichia coli, an intrinsically susceptible species. Third, the phenotypic impact of acquired AMP resistance genes heavily depends on the genetic background of the recipient bacteria. Taken together, functional compatibility with the new bacterial host emerges as a key factor limiting the genetic exchange of AMP resistance genes. Finally, our results suggest that AMPs induce highly specific changes in the composition of the human microbiota with implications for disease risks.

scholarly journals Wide occurrence of putative mobilized colistin resistance genes in the human gut microbiome

2021 ◽  
Author(s):  
Bruno G. N. Andrade ◽  
Tobias Goris ◽  
Haithem Afli ◽  
Felipe H. Coutinho ◽  
Alberto M.R. Davila ◽  
...  
Keyword(s):  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Genes ◽  
Human Populations ◽  
Clinical Settings ◽  
Genomic Context ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
High Incidence ◽  
Bacterial Genes

AbstractBackgroundThe high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin caused by MCR genes, poses an unprecedented threat to our civilization’s health. To diminish its impact, understanding the spread, evolution, and distribution among human populations should be a priority. To tackle this problem, we investigated the distribution and prevalence of potential mcr genes in the human gut microbiome by using a set of bioinformatics tools to screen for the presence of putative mcr genes (and co-located ARGs) in the Unified Human Gastrointestinal Genome (UHGG) collection, its genomic context, and phylogeny.ResultsA total of 2,079 ARGs were classified as different MCR in 2,046 Metagenome assembled genomes (MAGs), present in 1,596 individuals from 41 countries, of which 215 MCRs were identified in plasmidial contigs. The genera that presented the largest number of MCR-like genes were Suterella and Parasuterella, highly prevalent, and opportunistic pathogens. Other potential pathogens carrying MCR genes belonged to the genus Vibrio and Escherichia. Finally, we identified a total of 22,746 belonging to 21 different classes in the same 2,046 MAGs, suggesting multi-resistance potential, increasing the concern of its impact in the clinical settings.ConclusionThis study uncovers the diversity of MCR-like genes in the human gut microbiome. We showed the cosmopolitan distribution of these genes in patients worldwide and the co-presence of other antibiotic resistance genes, including ESBLs. Also, we described mcr-like genes encoded in the same ORF with PAP2-like in bacteria from the genus Sutterella. Although these novel sequences increase our knowledge about the diversity and evolution of mcr-like genes, their activity has to be experimentally validated in the future.

scholarly journals Host genetic and environmental factors shape the human gut resistome

2020 ◽  
Author(s):  
C.I. Le Roy ◽  
R.C. E. Bowyer ◽  
V.R. Carr ◽  
R. Costeira ◽  
J.E. Castillo-Fernandez ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Environmental Factors ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Antibiotic Resistance Genes ◽  
Environmental Exposures ◽  
Human Gut ◽  
Host Health ◽  
Host Genetic ◽  
Genetic And Environmental Factors

AbstractBackgroundUnderstanding and controlling the spread of antimicrobial resistance is one of the greatest challenges of modern medicine. To this end many efforts focus on characterising the human resistome or the set of antibiotic resistance determinants within the microbiome of an individual. Aside from antibiotic use, other host environmental and genetic factors that may shape the resistome remain relatively underexplored.MethodsUsing gut metagenome data from 250 TwinsUK female twins, we quantified known antibiotic resistance genes to estimate gut microbiome antibiotic resistance potential for 41 types of antibiotics and resistance mechanisms. Using heritability modelling, we assessed the influence of host genetic and environmental factors on the gut resistome. We then explored links between gut resistome, host health and specific environmental exposures using linear mixed effect models adjusted for age, BMI, alpha diversity and family structure.ResultsWe considered gut microbiome antibiotic resistance to 21 classes of antibiotics, for which resistance genes were detected in over 90% of our population sample. Using twin modelling, we estimated that on average about 25% of resistome variability could be attributed to host genetic influences. Greatest heritability estimates were observed for resistance potential to acriflavine (70%), dalfopristin (51%), clindamycin (48%), aminocoumarin (48%) and the total score summing across all antibiotic resistance genes (38%). As expected, the majority of resistome variability was attributed to host environmental factors specific to an individual. We compared antibiotic resistance profiles to multiple environmental exposures, lifestyle and health factors. The strongest associations were observed with alcohol and vegetable consumption, followed by high cholesterol medication and antibiotic usage. Overall, inter-individual variation in host environment showed modest associations with antibiotic resistance profiles, and host health status had relatively minor signals.ConclusionOur results identify host genetic and environmental influences on the human gut resistome. The findings improve our knowledge of human factors that influence the spread of antibiotic resistance genes and may contribute towards helping to attenuate it.

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

2019 ◽  
Author(s):  
Michael Baumgartner ◽  
Florian Bayer ◽  
Katia R. Pfrunder-Cardozo ◽  
Angus Buckling ◽  
Alex R. Hall
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Microbial Communities ◽  
Resistance Genes ◽  
Gut Microbiome ◽  
Individual Species ◽  
Human Gut ◽  
E Coli ◽  
Human Gut Microbiome ◽  
Resistance Evolution

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.

Antibiotic susceptibility profiles and frequency of resistance genes in clinical Shiga toxin-producing Escherichia coli isolates from Michigan over a 14-year period

2021 ◽  
Author(s):  
Sanjana Mukherjee ◽  
Heather M. Blankenship ◽  
Jose A. Rodrigues ◽  
Rebekah E. Mosci ◽  
James T. Rudrik ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Shiga Toxin ◽  
Antibiotic Susceptibility ◽  
Genetic Relatedness ◽  
Antibiotic Resistance Genes ◽  
Genomic Analysis ◽  
Mechanisms Of Resistance ◽  
Susceptibility Profiles

Background: Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogen that contributes to over 250,000 infections in the US each year. Because antibiotics are not recommended for STEC infections, resistance in STEC has not been widely researched despite an increased likelihood for the transfer of resistance gene from STEC to opportunistic pathogens residing within the same microbial community. Methods: Between 2001 and 2014, 969 STEC isolates were collected from Michigan patients. Serotyping and antibiotic susceptibility profiles to clinically relevant antibiotics were determined using disc diffusion, while epidemiological data was used to identify factors associated with resistance. Whole genome sequencing was used to examine genetic relatedness and identify genetic determinants and mechanisms of resistance in the non-O157 isolates. Results: Increasing frequencies of resistance to at least one antibiotic was observed over the 14 years (p=0.01). While the non-O157 serogroups were more commonly resistant than O157 (Odds Ratio: 2.4; 95% Confidence Interval:1.43-4.05), the frequency of ampicillin resistance among O157 isolates was significantly higher in Michigan compared to the national average (p=0.03). Genomic analysis of 321 non-O157 isolates uncovered 32 distinct antibiotic resistance genes (ARGs). Although mutations in genes encoding resistance to ciprofloxacin and ampicillin were detected in four isolates, most of the horizontally acquired ARGs conferred resistance to aminoglycosides, β-lactams, sulfonamides and/or tetracycline. Conclusions: This study provides insight into the mechanisms of resistance in a large collection of clinical non-O157 STEC isolates and demonstrates that antibiotic resistance among all STEC serogroups has increased over time, prompting the need for enhanced surveillance.

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