1. Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C
- Author
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Ilana L. Brito, Qiaojuan Shi, Albert C. Vill, Michael J. Satlin, and Alyssa G. Kent
- Subjects
Adult ,DNA, Bacterial ,0301 basic medicine ,Gene Transfer, Horizontal ,medicine.drug_class ,Science ,Antibiotics ,General Physics and Astronomy ,02 engineering and technology ,Drug resistance ,Biology ,Antimicrobial resistance ,Article ,General Biochemistry, Genetics and Molecular Biology ,Bacterial genetics ,03 medical and health sciences ,Human gut ,Antibiotic resistance ,Drug Resistance, Bacterial ,medicine ,Humans ,Microbiome ,lcsh:Science ,Gene ,030304 developmental biology ,Aged ,Genetics ,0303 health sciences ,Multidisciplinary ,030306 microbiology ,High-Throughput Nucleotide Sequencing ,General Chemistry ,Middle Aged ,021001 nanoscience & nanotechnology ,Anti-Bacterial Agents ,Gastrointestinal Microbiome ,Interspersed Repetitive Sequences ,Bacterial genes ,030104 developmental biology ,Genes, Bacterial ,Horizontal gene transfer ,lcsh:Q ,Metagenomics ,Mobile genetic elements ,0210 nano-technology ,Antibiotic resistance genes - Abstract
The gut microbiome harbors a ‘silent reservoir’ of antibiotic resistance (AR) genes that is thought to contribute to the emergence of multidrug-resistant pathogens through horizontal gene transfer (HGT). To counteract the spread of AR, it is paramount to know which organisms harbor mobile AR genes and which organisms engage in HGT. Despite methods that characterize the overall abundance of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) encoding AR genes. Here, we apply Hi-C, a high-throughput, culture-independent method, to surveil the bacterial carriage of MGEs. We compare two healthy individuals with seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics, and are acutely vulnerable to the threat of multidrug-resistant infections. We find distinct networks of HGT across individuals, though AR and mobile genes are associated with more diverse taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT occurs frequently over a several-week period in both cohorts. Whereas most efforts to understand the spread of AR genes have focused on pathogenic species, our findings shed light on the role of the human gut microbiome in this process., Linking antibiotic resistance (AR) in the gut microbiome with their bacterial hosts remains challenging. Here, the authors apply bacterial Hi-C to map mobile genetic elements in metagenomes, and illustrate that genes are present in more diverse taxa in neutropenic patients than healthy subjects.
- Published
- 2020