Exploring the Evolutionary Relationship Between Virulence and Drug Resistance

Abstract

One of the many possible negative outcomes of pathogen evolution is the emergence of a virulent drug resistant strain. A pathogen may exploit plasmid-mediated gene transfer to gain drug resistance and virulence genes in an attempt to become the exclusive infection. To answer questions on the possible emergence of a virulent drug resistant strain we constructed a nine dimensional SIS model with treatment. We used plasmid-mediated gene transfer by way of superinfection to distribute virulence and drug resistance genes. By examining the resulting system of differential equations at the two extremes of treatment level (%0 and %100), we determined the stability of the single strain endemic infection equilibrium points of interest. In the absence of treatment we determined a set of ancestral conditions which provided constraints on the model parameters. In the presence of treatment we focused on the ability of the virulent drug resistant (AB) strain to invade the avirulent drug resistant (B) strain. We were able to express these invasion conditions in terms of novel reproductive ratios that incorporated both non-superinfection effects and superinfection effects. Our model reveals that plasmid-mediated gene transfer by way of superinfection increases the parameter space allowing for virulence to evolve in a drug resistant population. However, virulence in a drug resistant population is not always more likely to evolve in comparison to virulence in a drug sensitive population.