Experimental approaches to phenotypic diversity in infection

Microbial infections are burdening human health, even after the advent of antibiotics, vaccines and hygiene. Thus, infection biology has aimed at the molecular understanding of the pathogen-host interaction. This has revealed key virulence factors, host cell signaling pathways and immune responses. However, our understanding of the infection process is still incomplete. Recent evidence suggests that phenotypic diversity can have important consequences for the infection process. Diversity arises from the formation of distinct subpopulations of pathogen cells (with distinct virulence factor expression patterns) and host cells (with distinct response capacities). For technical reasons, such phenotypic diversity has often been overlooked. We are highlighting several striking examples and discuss the experimental approaches available for analyzing the different subpopulations. Single cell reporters and approaches from systems biology do hold much promise.