title: Elevated CpxR~P levels repress the Ysc-Yop type III secretion system of Yersinia pseudotuberculosis.
abstract: One way that Gram-negative bacteria respond to extracytoplasmic stress is through the CpxA-CpxR system. An activated CpxA sensor kinase phosphorylates the CpxR response regulator to instigate positive auto-amplification of Cpx pathway activation, as well as synthesis of various bacterial survival factors. In the absence of CpxA, human enteropathogenic Yersinia pseudotuberculosis accumulates high CpxR~P levels aided by the action of low molecular weight phosphodonors such as acetyl~P. Critically, these bacteria are also defective for plasmid-encoded Ysc-Yop-dependent type III synthesis and secretion, an essential determinant of virulence. Herein, we investigated whether elevated CpxR~P levels account for lost Ysc-Yop function. Decisively, reducing CpxR∼P in Yersinia defective for CpxA phosphatase activity - through incorporating second-site suppressor mutations in ackA-pta or cpxR - dramatically restored Ysc-Yop T3S function. Moreover, the repressive effect of accumulated CpxR∼P is a direct consequence of binding to the promoter regions of the T3S genes. Thus, Cpx pathway activation has two consequences in Yersinia; one, to maintain quality control in the bacterial envelope, and the second, to restrict ysc-yop gene expression to those occasions where it will have maximal effect.
authors: Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden.
authors: Junfa
authors: J
authors: Liu
authors: Edvin J
authors: EJ
authors: Thanikkal
authors: Ikenna R
authors: IR
authors: Obi
authors: Matthew S
authors: MS
authors: Francis
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems; D015536:Down-Regulation; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D012097:Repressor Proteins / Q000378:metabolism*; D037521:Virulence Factors / Q000096:biosynthesis*; D015011:Yersinia pseudotuberculosis / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D012097:Repressor Proteins; D037521:Virulence Factors; C085504:CpxR protein, Bacteria