Contribution of the Cpx envelope stress system to metabolism and virulence regulation in Salmonella enterica serovar Typhimurium.

Authors:
Sivaraman Subramaniam, Volker S Müller, Nina A Hering, Hans Mollenkopf, Daniel Becker, Ann Kathrin Heroven, Petra Dersch, Anne Pohlmann, Karsten Tedin, Steffen Porwollik, Michael McClelland, Thomas F Meyer, Sabine Hunke
Year of publication:
2019
Volume:
14
Issue:
2
Issn:
1932-6203
Journal title abbreviated:
PLoS ONE
Journal title long:
PloS one
Impact factor:
2.740
Abstract:
The Cpx-envelope stress system regulates the expression of virulence factors in many Gram-negative pathogens. In Salmonella enterica serovar Typhimurium deletion of the sensor kinase CpxA but not of the response regulator CpxR results in the down regulation of the key regulator for invasion, HilA encoded by the Salmonella pathogenicity island 1 (SPI-1). Here, we provide evidence that cpxA deletion interferes with dephosphorylation of CpxR resulting in increased levels of active CpxR and consequently in misregulation of target genes. 14 potential operons were identified to be under direct control of CpxR. These include the virulence determinants ecotin, the omptin PgtE, and the SPI-2 regulator SsrB. The Tat-system and the PocR regulator that together promote anaerobic respiration of tetrathionate on 1,2-propanediol are also under direct CpxR control. Notably, 1,2-propanediol represses hilA expression. Thus, our work demonstrates for the first time the involvement of the Cpx system in a complex network mediating metabolism and virulence function.