The Perfect Condition for the Rising of Superbugs: Person-to-Person Contact and Antibiotic Use Are the Key Factors Responsible for the Positive Correlation between Antibiotic Resistance Gene Diversity and Virulence Gene Diversity in Human Metagenomes

Abstract

Human metagenomes with a high diversity of virulence genes tend to have a high diversity of antibiotic-resistance genes and vice-versa. To understand this positive correlation, we simulated the transfer of these genes and bacterial pathogens in a community of interacting people that take antibiotics when infected by pathogens. Simulations show that people with higher diversity of virulence and resistance genes took antibiotics long ago, not recently. On the other extreme, we find people with low diversity of both gene types because they took antibiotics recently—while antibiotics select specific resistance genes, they also decrease gene diversity by eliminating bacteria. In general, the diversity of virulence and resistance genes becomes positively correlated whenever the transmission probability between people is higher than the probability of losing resistance genes. The positive correlation holds even under changes of several variables, such as the relative or total diversity of virulence and resistance genes, the contamination probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the transmission between people and antibiotic usage are the leading causes for the positive correlation between virulence and antibiotic-resistance genes.

COVID-19 Lockdowns May Reduce Resistance Genes Diversity in the Human Microbiome and the Need for Antibiotics

“…Antibiotics are used as medicines to fight and eliminate bacterial infections, kill or inhibit their growth, and thus help the immune system resolve the disease [12][13][14]. In humans, antibiotic stewardship is dictated by bacterial infection, and, as such, the presence of bacterial pathogens can prompt an enrichment of human microbiomes with antibiotic resistance genes [7] whose expression enables bacteria to survive in the presence of these chemicals. Several examples in the literature on microbiome microbial dynamics are driven by human actions [15][16][17].…”

“…In each cycle, we considered all procedures described in the pseudocode (Figure 3). In addition, we used as default the parameterized values of our model [7]. The main steps of the program in each cycle are:…”

“…Human metagenomes with higher diversity of virulence genes tend to be precisely those with higher diversity of antibiotic-resistance genes [6], possibly facilitating the emergence of superbugs. However, the diversity of both gene types is dynamic over time, changing according to antibiotics usage and microbial transmission between people [7]. Bacterial transmission occurs between people that establish a network of contacts among them.…”

Are Virulence and Antibiotic Resistance Genes Linked? A Comprehensive Analysis of Bacterial Chromosomes and Plasmids

“…Previous research has shown that the diversity of virulence and antibiotic resistance genes correlate positively across human gut microbial communities and their genomes (metagenomes) [ 14 ]. In other words, metagenomes with a higher diversity of drug resistance genes are also the ones with a higher diversity of virulence genes, and vice versa—metagenomes with a lower diversity of drug resistance genes are also the ones with a lower diversity of virulence genes [ 15 ]. A previous work has shown that this positive correlation arises whenever the transmission probability of bacteria, along with their genes, between people is higher than the probability of losing resistance genes.…”

“…This is a likely relationship because fitness costs imposed by resistance determinants often disappear in a few tens or hundreds of generations after a new gene has arisen [ 16 , 17 , 18 ]. Therefore, the positive correlation did not arise due to co-selection by antibiotics on both gene types in the metagenome [ 15 ]. Human beings interact and exchange bacteria and resistance and virulence genes through physical contact—perhaps unexpectedly, individuals with a higher diversity of both gene types are the ones that have not taken antibiotics for a long time.…”