Phenotypic Heterogeneity in Pathogens

Pathogen diversity within an infected organism has traditionally been explored through the lens of genetic heterogeneity. Hallmark studies have characterized how genetic diversity within pathogen subpopulations contributes to treatment escape and infectious disease progression. However, recent studies have begun to reveal the mechanisms by which phenotypic heterogeneity is established within genetically identical populations of invading pathogens. Furthermore, exciting new work highlights how these phenotypically heterogeneous subpopulations contribute to a pathogen population better equipped to handle the complex and fluctuating environment of a host organism. In this review, we focus on how bacterial pathogens, including Staphylococcus aureus, Salmonella typhimurium, Pseudomonas aeruginosa, and Mycobacterium tuberculosis, establish and maintain phenotypic heterogeneity, and we explore recent work demonstrating causative links between this heterogeneity and infection outcome.