The Bacterial Mobile Resistome Transfer Network Connecting the Animal and Human Microbiomes

Abstract

Horizontally acquired antibiotic resistance genes (ARGs) in bacteria are highly mobile and have been ranked as principal risk resistance determinants. However, the transfer network of the mobile resistome and the forces driving mobile ARG transfer are largely unknown. Here, we present the whole profile of the mobile resistome in 23,425 bacterial genomes and explore the effects of phylogeny and ecology on the recent transfer (>99% nucleotide identity) of mobile ARGs. We found that mobile ARGs are mainly present in four bacterial phyla and are significantly enriched in Proteobacteria. The recent mobile ARG transfer network, which comprises 703 bacterial species and 16,859 species pairs, is shaped by the bacterial phylogeny, while an ecological barrier also exists, especially when interrogating bacteria colonizing different human body sites. Phylogeny is still a driving force for the transfer of mobile ARGs between farm animals and the human gut, and, interestingly, the mobile ARGs that are shared between the human and animal gut microbiomes are also harbored by diverse human pathogens. Taking these results together, we suggest that phylogeny and ecology are complementary in shaping the bacterial mobile resistome and exert synergistic effects on the development of antibiotic resistance in human pathogens. IMPORTANCEThe development of antibiotic resistance threatens our modern medical achievements. The dissemination of antibiotic resistance can be largely attributed to the transfer of bacterial mobile antibiotic resistance genes (ARGs). Revealing the transfer network of these genes in bacteria and the forces driving the gene flow is of great importance for controlling and predicting the emergence of antibiotic resistance in the clinic. Here, by analyzing tens of thousands of bacterial genomes and millions of human and animal gut bacterial genes, we reveal that the transfer of mobile ARGs is mainly controlled by bacterial phylogeny but under ecological constraints. We also found that dozens of ARGs are transferred between the human and animal gut and human pathogens. This work demonstrates the whole profile of mobile ARGs and their transfer network in bacteria and provides further insight into the evolution and spread of antibiotic resistance in nature.A ntibiotic resistance is a growing global threat to human public health, and the continuing emergence of drug-resistant bacteria has led to the potential for a postantibiotic era (1). Bacteria have evolved a dynamic array of antimicrobial resistance mechanisms to withstand antibiotic attacks, such as altering drug target(s), synthesizing drug-inactivating enzymes, changing cell membrane permeability, and exporting drugs via efflux pumps (2). A large number of antibiotic resistance genes (ARGs) involved in these resistance mechanisms have been discovered and are collected in various ARG databases, including ARG-ANOTT (3), CARD (4), ResFinder (5), and ARDB (6). Because antibiotic resistance can be endogenous or exogenous, ARGs are generally classified as intrins...

TCDD influences reservoir of antibiotic resistance genes in murine gut microbiome

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MCR-1.6, a New MCR Variant Carried by an IncP Plasmid in a Colistin-Resistant Salmonella enterica Serovar Typhimurium Isolate from a Healthy Individual

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Isothermal assay targeting class 1 integrase gene for environmental surveillance of antibiotic resistance markers

“…Selective reduction of ARGs using anaerobic digestion also correlated with reduced counts of the intI1 gene (Burch et al, 2016). Determined via whole genome sequence analysis of 23,425 bacterial genomes (Hu et al, 2016), the sulfonamide resistance gene sul1 , which is typically associated with intI1 (Luo et al, 2010), was observed with the greatest number of different ARGs types. As such, the high correlation between the intI1 gene LAMP assay and abundance of ARGs indicates its utility for monitoring ARGs in river samples.…”