Defeating Drug Resistance in Pathogens: Guidance from Evolutionary Theory

Many of the greatest challenges in medicine and public health involve the evolution of drug resistance by pathogenic microbes. Recent advances in the theory of natural selection suggest there are two broad classes of pathogen traits that can be targeted by drugs or vaccines. The first class, consisting of traits that benefit the individual pathogen cell produces a strong evolutionary response and the rapid emergence of pathogen resistance. The second class, consisting of group-beneficial traits, produces a weaker evolutionary response and less drug resistance. While most previous drug development has targeted the first class, it would be advantageous to focus on the second class as targets for drug and vaccine development. Specific examples and test cases are discussed.