A resistome roadmap: from the human body to pristine environments

Abstract

A comprehensive characterization of the human body resistome (sets of antibiotic resistance genes (ARGs)) is yet to be done and paramount for addressing the antibiotic microbial resistance threat. Here, we study the resistome of 771 samples from five major body parts (skin, nares, vagina, gut and oral cavity) of healthy subjects from the Human Microbiome Project and addressed the potential dispersion of ARGs in pristine environments. A total of 28,731 ARGs belonging to 344 different ARG types were found in the HMP proteome dataset (n=9.1x107 proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high inter-individual variability. Nares had the highest ARG load ({approx}5.4 genes/genome) followed by the oral cavity, while the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance ({approx}1.3 genes/genome). Fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide-lincosamide-streptogramin (MLS) or tetracycline. Most of the ARGs belonged to common bacterial commensals and multidrug resistance trait was predominant in the nares and vagina. Our data also provide hope, since the spread of common ARG from the human body to pristine environments (n=271 samples; 77 Gb of sequencing data and 2.1x108 proteins analyzed) thus far remains very unlikely (only one case found in an autochthonous bacterium from a pristine environment). These findings broaden our understanding of ARG in the context of the human microbiome and the One-Health Initiative of WHO uniting human host-microbes and environments as a whole. ImportanceThe current antibiotic resistance crisis affects our health and wealth at a global scale and by 2050 predictions estimate 10 million deaths attributed to antibiotic resistance worldwide. Remarkably, a comprehensive analysis of ARG diversity and prevalence in different human body sites is yet to be done. Undoubtedly, our body and human built-environment have antibiotic resistant bacteria than can also be transported to other environments. Hence, the analysis of Human Microbiome Project dataset provides us not only the opportunity to explore in detail the ARGs diversity and prevalence in different parts of our body but also to provide some insights into the dispersion of ARGs from human to natural populations inhabiting pristine environments. Thus, our data would help to stablish a baseline in ARG surveillance protocols to asses further changes in antibiotic resistances in our society.