Person-to-person contagion and antibiotic usage are the key factors responsible for the positive correlation between antibiotic resistance gene diversity and virulence gene diversity in human metagenomes

Antibiotics have been used on a large scale in veterinary and medical contexts. The massive and continuous exposure to antimicrobial drugs has led to the emergence and spread of antibiotic resistance, which is nowadays one of the greatest threats to public health. This study aims to understand the cause of the recently shown positive correlation between the diversity of antibiotic resistance genes and the diversity of pathogenicity genes across human metagenomes from different geographical origins. Using computer simulations, we studied the effect of several factors, such as the total diversity of virulence genes and antibiotic resistance genes, the contagion probability between individuals, the loss rate of resistance genes, whether or not the population uses antibiotics, or the contacts’ network between people (regular, small-world, and random networks). Our results show that the key factor for the emergence of the positive correlation is the ratio between the contagion probability between individuals and the loss rate of resistance genes. Importantly, if the contagion probability is higher than the loss rate of resistance genes, the positive correlation emerges. We argue that the loss rate of resistance genes may be very low, or even null, leaving contagion probability between people as the main cause for the establishment of a positive correlation between the diversity of antibiotic resistance genes and the diversity of pathogenicity genes across human metagenomes. Therefore, something as prosaic as the contagion between people implies that those humans with higher diversity of virulence genes in their metagenomes are, precisely, those expected to have a high diversity of resistance genes. This is unfortunate because these people with higher diversity of virulence genes are precisely those more plausible to take antibiotics, so the drug is unlikely to be useful.