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Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C

View ORCID ProfileAlyssa Kent, View ORCID ProfileAlbert Vill, Qiaojuan Shi, View ORCID ProfileMichael J. Satlin, View ORCID ProfileIlana Lauren Brito
doi: https://doi.org/10.1101/2020.03.19.998526
Alyssa Kent
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY
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Albert Vill
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY
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Qiaojuan Shi
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY
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Michael J. Satlin
2Department of Internal Medicine, Weill Cornell Medicine, New York, NY
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Ilana Lauren Brito
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY
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  • For correspondence: ibrito@cornell.edu
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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 the process of horizontal gene transfer (HGT). To counteract the spread of AR genes, it is paramount to know which organisms harbor mobile AR genes and with which organisms they engage in HGT. Despite methods to characterize the bulk presence1, abundance2 and function3 of AR genes in the gut, technological limitations of short-read sequencing have precluded linking bacterial taxa to specific mobile genetic elements (MGEs) and their concomitant AR genes. Here, we apply and evaluate a high-throughput, culture-independent method for surveilling the bacterial carriage of MGEs, based on bacterial Hi-C protocols. We compare two healthy individuals with a cohort of seven neutropenic patients undergoing hematopoietic stem cell transplantation, who receive multiple courses of antibiotics throughout their prolonged hospitalizations, and are thus acutely vulnerable to the threat of multidrug-resistant infections4. We find that the networks of HGT are surprisingly distinct between individuals, yet AR and mobile genes are more dispersed across taxa within the neutropenic patients than the healthy subjects. Our data further suggest that HGT is occurring throughout the course of treatment in the microbiomes of neutropenic patients and within the guts of healthy individuals over a similar timeframe. 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.

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Posted March 20, 2020.
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Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C
Alyssa Kent, Albert Vill, Qiaojuan Shi, Michael J. Satlin, Ilana Lauren Brito
bioRxiv 2020.03.19.998526; doi: https://doi.org/10.1101/2020.03.19.998526
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Widespread transfer of mobile antibiotic resistance genes within individual gut microbiomes revealed through bacterial Hi-C
Alyssa Kent, Albert Vill, Qiaojuan Shi, Michael J. Satlin, Ilana Lauren Brito
bioRxiv 2020.03.19.998526; doi: https://doi.org/10.1101/2020.03.19.998526

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