Non-Darwinian Selection of Plasmid-Mediated Antibiotic Resistance

Abstract

Resistance of bacteria to antibiotics is an inevitable consequence of long-term exposure to sub lethal drug concentrations, and the problem has been greatly exacerbated by inappropriate use. Resistance can be conferred by chromosomal mutations that are passed on in normal cell division (vertical gene transfer) or by horizontal gene transfer processes such as conjugation. Darwinian natural selection implies that individual organisms possessing a survival advantage over their peers will represent an increasing proportion of the total population in subsequent generations. Using the techniques of evolutionary dynamics, we have modelled the selection of antibiotic resistant strains of bacteria resulting from either vertical or horizontal gene transfer, and the consequences of these events for drug sensitivity. Our model suggests that the dynamics of horizontal gene transfer are such that plasmid-bearing bacteria may dominate a population despite having a growth disadvantage compared to the same bacteria that do not carry the plasmid. Horizontal gene transfer than by vertical transfer propagates antibiotic resistance more rapidly. These findings have implications for the design of combination drug regimens for treatment of bacterial infections.