Antibiotic Resistance Gene Diversity and Virulence Gene Diversity Are Correlated in Human Gut and Environmental Microbiomes

Abstract

Human beings have used large amounts of antibiotics, not only in medical contexts but also, for example, as growth factors in agriculture and livestock, resulting in the contamination of the environment. Even when pathogenic bacteria are the targets of antibiotics, hundreds of nonpathogenic bacterial species are affected as well. Therefore, both pathogenic and nonpathogenic bacteria have gradually become resistant to antibiotics. We tested whether there is still cooccurrence of resistance and virulence determinants. We performed a comparative study of environmental and human gut metagenomes from different individuals and from distinct human populations across the world. We found a great diversity of antibiotic resistance determinants (AR diversity [ARd]) and virulence factors (VF diversity [VFd]) in metagenomes. Importantly there is a correlation between ARd and VFd, even after correcting for protein family richness. In the human gut, there are less ARd and VFd than in more diversified environments, and yet correlations between the ARd and VFd are stronger. They can vary from very high in Malawi, where antibiotic consumption is unattended, to nonexistent in the uncontacted Amerindian population. We conclude that there is cooccurrence of resistance and virulence determinants in human gut microbiomes, suggesting a possible coselective mechanism.IMPORTANCE Every year, thousands of tons of antibiotics are used, not only in human and animal health but also as growth promoters in livestock. Consequently, during the last 75 years, antibiotic-resistant bacterial strains have been selected in human and environmental microbial communities. This implies that, even when pathogenic bacteria are the targets of antibiotics, hundreds of nonpathogenic bacterial species are also affected. Here, we performed a comparative study of environmental and human gut microbial communities issuing from different individuals and from distinct human populations across the world. We found that antibiotic resistance and pathogenicity are correlated and speculate that, by selecting for resistant bacteria, we may be selecting for more virulent strains as a side effect of antimicrobial therapy.

Keywords: antibiotic resistance; cooccurrence; human gut; metagenomics; microbiome; virulence.