Sequence type diversity amongst antibiotic-resistant bacterial strains is lower than amongst antibiotic-susceptible strains

Abstract

The increasing number of antibiotic resistant bacterial infections is a global threat to human health. Antibiotic resistant bacterial strains generally evolve from susceptible strains by either horizontal gene transfer or chromosomal mutations. After evolving within a host, such resistant strains can be transmitted to other hosts and increase in frequency in the population at large. Population genetic theory postulates that the increase in frequency of an adaptive trait can lead to signatures of selective sweeps. One would thus expect to observe reduced genetic diversity amongst that part of the population that carries the adaptive trait. Specifically, if the evolution of new resistant strains is rare, it is expected that resistant strains represent only a subset of the diversity of susceptible strains. It is currently unknown if diversity of resistant strains is indeed lower than diversity of susceptible strains when considering antibiotic resistance. Here we show that in several bacterial species in several different datasets, sequence-type diversity amongst antibiotic-resistant bacterial strains is indeed lower than amongst antibiotic-susceptible strains in most cases. We re-analysed eight existing clinical datasets with Escherichia coli, Staphylococcus aureus and Enterococcus faecium samples. These datasets consisted of 53 - 1094 patient samples, with multi-locus sequence types and antibiotic resistance phenotypes for 3 - 19 different antibiotics. Out of 59 comparisons, we found that resistant strains were significantly less diverse than susceptible strains in 51 cases (86%). In addition, we show that sequence-type diversity of antibiotic-resistant strains is lower if resistance is rare, compared to when resistance is common, which is consistent with rare resistance being due to fewer evolutionary origins. Our results show that for several different bacterial species, we observe reduced diversity of resistant strains, which is consistent with the evolution of resistance driven by selective sweeps stemming from a limited number of evolutionary origins. In future studies, more detailed analysis of such sweep signatures is warranted.