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 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 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 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 Polyphenol utilization proteins in human gut microbiome

2021 ◽  
Author(s):  
Bo Zheng ◽  
Yinchao He ◽  
Pengxiang Zhang ◽  
Yi-Xin Huo ◽  
Yanbin Yin
Keyword(s):  
Human Health ◽  
Gut Microbiome ◽  
Sequence Similarity ◽  
Gene Clusters ◽  
Metagenomic Data ◽  
Human Populations ◽  
Human Gut ◽  
Systematic Classification ◽  
Dietary Polyphenols ◽  
Human Gut Microbiome

Dietary polyphenols can significantly benefit human health, but their bioavailability is metabolically controlled by human gut microbiota. To facilitate the study of polyphenol metabolism for human gut health, we have manually curated experimentally characterized polyphenol utilization proteins (PUPs) from published literature. This resulted in 60 experimentally characterized PUPs (named seeds) with various metadata, such as species and substrate. Further database search found 107,851 homologs of the seeds from UniProt and UHGP (Unified Human Gastrointestinal Protein) databases. All PUP seeds and homologs were classified into protein classes, families and subfamilies based on Enzyme Commission (EC) numbers, Pfam (protein family) domains and sequence similarity networks. By locating PUP homologs in the genomes of UHGP, we have identified 1,074 physically linked PUP gene clusters (PGCs), which are potentially involved in polyphenol metabolism in the human gut. The gut microbiome of Africans was consistently ranked the top in terms of the abundance and prevalence of PUP homologs and PGCs among all geographical continents. This reflects the fact that dietary polyphenols are more commonly consumed by African population than other populations such as Europeans and North Americans. A case study of the Hadza hunter-gatherer microbiome verified the feasibility of using dbPUP to profile metagenomic data for biologically meaningful discovery, suggesting an association between diet and PUP abundance. A Pfam domain enrichment analysis of PGCs identified a number of putatively novel PUP families. Lastly, a user-friendly web interface ( https://bcb.unl.edu/dbpup/ ) provides all the data online to facilitate the research of polyphenol metabolism for improved human health. Importance Long-term consumption of polyphenol-rich foods have been shown to lower the risk of various human diseases such as cardiovascular diseases, cancers, and metabolic diseases. Raw polyphenols are often enzymatically processed by gut microbiome, which encode various polyphenol utilization proteins (PUPs) to produce metabolites with much higher bioaccessibility to gastrointestinal cells. This study delivered dbPUP as an online database for experimentally characterized PUPs and their homologs in human gut microbiome. This work also performed a systematic classification of PUPs into enzyme classes, families, and subfamilies. The signature Pfam domains were identified for PUP families, enabling conserved domain-based PUP annotation. This standardized sequence similarity-based PUP classification system offered a guideline for the future inclusion of new experimentally characterized PUPs and the creation of new PUP families. An in-depth data analysis was further conducted on PUP homologs and physically linked PUP gene clusters (PGCs) in gut microbiomes of different human populations.

scholarly journals A unified sequence catalogue of over 280,000 genomes obtained from the human gut microbiome

2019 ◽  
Author(s):  
Alexandre Almeida ◽  
Stephen Nayfach ◽  
Miguel Boland ◽  
Francesco Strozzi ◽  
Martin Beracochea ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Functional Characterization ◽  
Genomic Variation ◽  
Human Populations ◽  
Single Nucleotide Variants ◽  
Human Gut ◽  
Large Reservoir ◽  
Functional Annotations ◽  
Human Gut Microbiome ◽  
Gene Catalogue

AbstractComprehensive reference data is essential for accurate taxonomic and functional characterization of the human gut microbiome. Here we present the Unified Human Gastrointestinal Genome (UHGG) collection, a resource combining 286,997 genomes representing 4,644 prokaryotic species from the human gut. These genomes contain over 625 million protein sequences used to generate the Unified Human Gastrointestinal Protein (UHGP) catalogue, a collection that more than doubles the number of gut protein clusters over the Integrated Gene Catalogue. We find that a large portion of the human gut microbiome remains to be fully explored, with over 70% of the UHGG species lacking cultured representatives, and 40% of the UHGP missing meaningful functional annotations. Intra-species genomic variation analyses revealed a large reservoir of accessory genes and single-nucleotide variants, many of which were specific to individual human populations. These freely available genomic resources should greatly facilitate investigations into the human gut microbiome.

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 Bacterial associations in the healthy human gut microbiome across populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mark Loftus ◽  
Sayf Al-Deen Hassouneh ◽  
Shibu Yooseph
Keyword(s):  
Gut Microbiome ◽  
Sequence Data ◽  
Bacterial Species ◽  
Human Populations ◽  
Human Gut ◽  
Healthy Human ◽  
Human Gut Microbiome ◽  
Genome Shotgun Sequence ◽  
Bacterial Associations ◽  
And Function

AbstractIn a microbial community, associations between constituent members play an important role in determining the overall structure and function of the community. The human gut microbiome is believed to play an integral role in host health and disease. To understand the nature of bacterial associations at the species level in healthy human gut microbiomes, we analyzed previously published collections of whole-genome shotgun sequence data, totaling over 1.6 Tbp, generated from 606 fecal samples obtained from four different healthy human populations. Using a Random Forest Classifier, we identified 202 signature bacterial species that were prevalent in these populations and whose relative abundances could be used to accurately distinguish between the populations. Bacterial association networks were constructed with these signature species using an approach based on the graphical lasso. Network analysis revealed conserved bacterial associations across populations and a dominance of positive associations over negative associations, with this dominance being driven by associations between species that are closely related either taxonomically or functionally. Bacterial species that form network modules, and species that constitute hubs and bottlenecks, were also identified. Functional analysis using protein families suggests that much of the taxonomic variation across human populations does not foment substantial functional or structural differences.

scholarly journals The Metabolism of Glucosinolates by Gut Microbiota

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2750
Author(s):  
Kalina Sikorska-Zimny ◽  
Luciano Beneduce
Keyword(s):  
Gut Microbiome ◽  
Enzymatic Reaction ◽  
Human Populations ◽  
Enzymatic Reactions ◽  
Plant Metabolites ◽  
Human Gut ◽  
Secondary Plant Metabolites ◽  
Human Gut Microbiome ◽  
Beneficial Effects ◽  
Anti Cancer

Glucosinolates (GLS) and their derivatives are secondary plant metabolites abundant in Brassicaceae. Due to the enzymatic reaction between GLS and myrosinase enzyme, characteristic compounds with a pungent taste are formed, used by plants to defend themselves against insect herbivores. These GLS derivatives have an important impact on human health, including anti-inflammation and anti-cancer effects. However, GLS derivatives’ formation needs previous enzymatic reactions catalyzed by myrosinase enzyme. Many of the brassica-based foods are processed at a high temperature that inactivates enzymes, hindering its bioavailability. In the last decade, several studies showed that the human gut microbiome can provide myrosinase activity that potentially can raise the beneficial effects of consumption of vegetables rich in GLS. The variability of the human gut microbiome (HGM) in human populations and the diverse intake of GLS through the diet may lead to greater variability of the real dose of pro-healthy compounds absorbed by the human body. The exploitation of the genetic and biochemical potential of HGM and correct ecological studies of both isolated strains and mixed population are of great interest. This review focuses on the most recent advances in this field.

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