The regulatory protein PhoP controls susceptibility to the host inflammatory response in Shigella flexneri

The PhoP/PhoQ two-component regulatory system controls transcription of sev eral key virulence genes essential for Salmonella survival in the host cell phagosome. Here, we determine that the PhoP/PhoQ system also regulates vir ulence in the aetiological agent of bacillary dysentery, Shigella flexneri, even though this pathogen escapes from the phagosome into the cytoplasm of the host cell. A phoP mutant of Shigella established infections and induce d an acute inflammatory response in two different animal models. However, i nfections with phoP mutant bacteria were resolved more rapidly than infecti ons with wild-type Shigella. Moreover, the Shigella phoP mutant was more se nsitive than the wild-type strain to killing by polymorphonuclear leucocyte s (PMNs), cationic polypeptides extracted from PMNs and other animal-derive d antimicrobial peptides. The phoP mutant, however, invaded epithelial cell s, spread intercellularly, induced apoptosis in macrophages and tolerated e xtreme acid pH as efficiently as the wild-type strain. PhoP appears to regu late Shigella susceptibility to PMNs and antimicrobial molecules that are i mportant for the late stages of infection with this enteric bacterium.