Elevated CpxR∼P levels repress the Ysc–Yop type III secretion system of Yersinia pseudotuberculosis

• Published in: Research in microbiology 2012-09, Vol.163 (8), p.518-530
• Main Authors: Liu, Junfa, Thanikkal, Edvin J., Obi, Ikenna R., Francis, Matthew S.
• Format: Article
• Language: English
• Subjects: AckA; Bacterial Proteins - metabolism; Bacterial Secretion Systems; Bacteriology; Biological and medical sciences; CpxA; Down-Regulation; Extracytoplasmic stress; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; Humans; Microbiology; mikrobiologi; Miscellaneous; Molecular Biology; molekylärbiologi; Pta; Repressor Proteins - metabolism; Virulence; Virulence Factors - biosynthesis; Yersinia pseudotuberculosis - genetics
• ISSN: 0923-2508; 1769-7123; 1769-7123
• DOI: 10.1016/j.resmic.2012.07.010

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.