Regulation of Phenotypic Heterogeneity in Salmonella: Bifunctional Regulators, RcsB and YifA, Shape Flagellar Bistability

Abstract

Heterogeneous expression of flagellar and invasion genes is crucial for Salmonella virulence. Such a division of labor enables an invasive subpopulation to trigger inflammation in the infected host and alter the gut environment to favor growth of Salmonella. Meanwhile, nonflagellated cells are better able to evade host defenses systemically and persist. This bistable expression requires the master regulator of the flagellar cascade, FlhD4C2, to be kept in low concentration by post-translational regulators YdiV, ClpXP, and STM14_2047. In this study, we demonstrated novel roles for two previously identified regulators of flagellar expression. RcsB and YifA are independently able to repress the transcription of both flhDC and STM14_2047 in several conditions, but their control of flagellar expression is environmentally responsive. We have identified conditions where RcsB and YifA act as either repressors or promoters of flagellar expression and hypothesize that this conditional regulation increases fitness in varied environments.