bioRxiv preprint doi: https://doi.org/10.1101/2021.04.26.441444; this version posted April 27, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Bacteroidales species are a reservoir of phase-variable antibiotic resistance genes in the human gut microbiome Wei Yana, A. Brantley Hallb,c, and Xiangfang Jianga a National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA b Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland, USA c Center for Bioinformatics and Computational Biology, University of Maryland, College Park, Maryland, USA Address correspondence to Xiaofang Jiang:
[email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.04.26.441444; this version posted April 27, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT Phase-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.