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 (HMP) and addressed the potential dispersion of ARGs in pristine environments. A total of 28,714 ARGs belonging to 235 different ARG types were found in the HMP proteome dataset (n = 9.1 × 107 proteins analyzed). Our study reveals a distinct resistome profile (ARG type and abundance) between body sites and high interindividual variability. Nares had the highest ARG load (≈5.4 genes/genome) followed by the oral cavity, whereas the gut showed one of the highest ARG richness (shared with nares) but the lowest abundance (≈1.3 genes/genome). The fluroquinolone resistance genes were the most abundant in the human body, followed by macrolide–lincosamide–streptogramin (MLS) or tetracycline. Most ARGs belonged to common bacterial commensals and multidrug resistance trait were predominant in the nares and vagina. Many ARGs detected here were considered as low risk for human health, whereas only a few of them, such as BlaZ, dfrA14, dfrA17, or tetM, were classified as high-risk ARG. 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 2.1 × 108 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.

Metagenomic airborne resistome from urban hot spots through the One Health lens

“…From those contigs, ORFs were predicted using Prodigal (Hyatt et al, 2010 ). ARGs were annotated by comparing the ARG databases ARG_ANNOT (Gupta et al, 2014 ), RESFAMS (Gibson et al, 2015 ), and CARD (Jia et al, 2017 ) with both the assembled (ORFs) and unassembled (reads) data using blast (Maestre‐Carballa et al, 2019 , 2022 ). Only the best hits with a bit‐score ≥ 70, e‐value <10 −5 , and identities ≥50% or ≥ 90% (both thresholds were initially compared selecting later the cut‐off of ≥90% as likely the most reliable) were considered as potential ARG.…”

“…Only the best hits with a bit‐score ≥ 70, e‐value <10 −5 , and identities ≥50% or ≥ 90% (both thresholds were initially compared selecting later the cut‐off of ≥90% as likely the most reliable) were considered as potential ARG. The housekeeping genes present in the used ARGs databases were not considered in our metagenomic analysis due to the difficulty of determining if they were bona fide ARGs using our thresholds (Maestre‐Carballa et al, 2022 ) According to the database CARD (Jia et al, 2017 ) or the nr database (NCBI), the detected ARG were grouped by the antibiotic they confer resistance to. ARG abundance and normalisation were estimated by dividing the total number of ARGs per Gb of metagenome (assembled or unassembled) and if necessary, by volume sample as well.…”

One Earth: The Equilibrium between the Human and the Bacterial Worlds

“…It was found that nares had the highest load of ARGs (~5.4 genes per genome), followed by the oral cavity, whereas the gut exhibited the lowest abundance (~1.3 genes per genome). Interestingly, the transfer of common ARGs from humans to pristine environments seemed to be very low or nonexistent [35]. The antibiotic resistome is dynamic and, at present, still expanding [16].…”

Old Folks, Bad Boon: Antimicrobial Resistance in the Infant Gut Microbiome

“…[ 55 ] in the vagina. Cabralla-Maestre and co-workers [ 56 ] reported that tetracycline resistance genes were the most frequent ARGs in the vagina of healthy non-pregnant women, followed by multidrug resistance genes. In comparison with the gut resistome, the vagina has a lower diversity in terms of antibiotic resistance [ 54 , 57 ].…”