Functional characterization of the antibiotic resistance reservoir in the human microflora

By M. Sommer, Gautam Dantas, George M. Church. Science, 2009

875 citations recorded by the source corpus.

Hidden Pockets of Resistance Groups of bacteria indulge in gene swapping at frequencies correlated with prevailing selection pressures and phylogenetic relatedness. When assaulted by antibiotics, antibiotic resistance genes become favored currency for exchange among bacteria. During sequencing of human gut microflora, Sommer et al. (p. 1128) found a very large reservoir of distinct genes that, when put into Escherichia coli, conferred resistance to a wide range of drugs. By contrast, analysis of the culturable aerobic gut microbiome, which constitutes a tiny fraction of the entire gut flora, revealed resistance genes highly similar to those harbored by human pathogens. Although there is a risk of novel modes of antibiotic resistance emerging from this reservoir, because they are evolutionarily distant, gene transfer between pathogens and the poorly known majority of the microbiome might actually be quite restricted. Large numbers of previously unidentified antibiotic resistance genes occur in gut bacteria. To understand the process by which antibiotic resistance genes are acquired by human pathogens, we functionally characterized the resistance reservoir in the microbial flora of healthy individuals. Most of the resistance genes we identified using culture-independent sampling have not been previously identified and are evolutionarily distant from known resistance genes. By contrast, nearly half of the resistance genes we identified in cultured aerobic gut isolates (a small subset of the gut microbiome) are identical to resistance genes harbored by major pathogens. The immense diversity of resistance genes in the human microbiome could contribute to future emergence of antibiotic resistance in human pathogens.

Subfields: Food Science, Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/95e1f497230f6a5ccfca311b4a0e8a4b29cf8cd0

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Citations in the corpus

Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances (2016, background): “…the resistance genes identified in human gut isolates are identical at the nucleotide level to resistance genes from human pathogenic Frontiers in Microbiology | www.frontiersin.org 5 January 2016 | Volume 6 | Article 1543 mechanisms are shown in pink-shaded boxes. isolates (Sommer et al., 2009).”
Long-term impacts of antibiotic exposure on the human intestinal microbiota. (2010, background): “Sommer et al. (2009) characterized the functional resistance reservoir in two unrelated healthy subjects who had not been exposed to antibiotics for at least 1 year.”
Dissemination of Antimicrobial Resistance in Microbial Ecosystems through Horizontal Gene Transfer (2016, background): “…or activated sludge (Mori et al., 2008; Parsley et al., 2010), as well as in the microbiota of animals (Kazimierczak et al., 2009; Wichmann et al., 2014) and humans (Sommer et al., 2009; Cheng et al., 2012;Moore et al., 2013, 2015; Card et al., 2014; Fouhy et al., 2014; Clemente et al., 2015).”
Antibiotic resistance in the environment: a link to the clinic? (2010, result): “This is consistent with a study by the Church group that investigated both culturable bacteria and gut metagenomic libraries from two human volunteers that showed that commensal microbes harbored a large number of antibiotic resistance elements [43].”
Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. (2012, background): “Ce persist in the human host environment even in the absence of selective pressure (Karami et al., 2007; Sommer et al., 2009).”
Antimicrobial resistance in humans, livestock and the wider environment (2015, neutral): “One study found numerous resistance genes in the unculturable fraction, the so-called microbial ‘dark matter’ that comprises the bulk of the gut flora, but these were not homologous with resistance genes of clinical relevance [5].”
Origins of bacterial diversity through horizontal genetic transfer and adaptation to new ecological niches. (2011, background): “Sommer et al. (2009) recently expressed DNA cloned from the human microbiome and selected clones for resistance to various antibiotics.”
Impact of antibiotics on the human microbiome and consequences for host health (2022, background): “Similarly, ARGs in healthy humans have been reported despite the absence of antibiotic use (Bengtsson‐Palme et al., 2015; Sommer et al., 2009; de Vries et al., 2011).”
Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation (2010, background): “One is the spread of antibiotic resistance among pathogens, which is facilitated by transfer from and between mutualists (4, 5).”
Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology (2014, background): “, 2010), human gut and oral microbiomes (Diaz-Torres et al., 2003, 2006; Sommer et al., 2009; Cheng et al., 2012) and animal gut microbiomes (Kazimierczak et al.”
Machine Learning Meta-analysis of Large Metagenomic Datasets: Tools and Biological Insights (2016, background): “More recently, shotgun metagenomics [19] provided expanded resolution to the level of microbial species [20-22] and strain [23], to the fungal and viral kingdoms [24], and to the level of individual genes across the metagenome [25,26].”
The Impact of the Gut Microbiota on Human Health: An Integrative View (2012, neutral): “The repeated use of antibiotics in humans has been hypothesized to increase the reservoir of antibioticresistant genes in our own microbiome (Sommer et al., 2009).”
Antibiotic resistance and its cost: is it possible to reverse resistance? (2010, background): “The threat from antibiotics that are released into the environment is illustrated by the existence of a large reservoir of resistance genes in the human microflora that could potentially serve as donors for the transfer of resistance to human pathogen”