Phenotypic Diversification of Microbial Pathogens-Cooperating and Preparing for the Future.

Recent studies revealed an amazing phenotypic heterogeneity between genetically identical individual cells within populations of microbial pathogens. During the course of an infection, subpopulations occur, which differ in certain virulence-relevant factors, stress adaptation functions or physiological and metabolic abilities. The mechanisms driving this heterogeneity are divergent reactions of the pathogens to differences in host tissue microenvironments. In addition, certain genetic regulatory circuits with positive feedback loops and stochastic differences in gene expression can generate endogenous fluctuations in regulatory components leading to bistable expression of virulence-associated functions. Here, we focus on the occurrence of phenotypic heterogeneity in populations of well-studied examples of pathogens, which enables cooperative, social behavior where a subpopulation of producers shares fitness- and/or virulence-relevant goods and traits with non-producers. We further highlight that this strategy allows preadaptation of a subgroup of cells to recurrent and thus predictable changes of the environment that they encounter during the different stages of the infection. The diversity within bacterial communities has a significant influence on the survival of the pathogens within their hosts and the progression of the disease.