Role of the two-component regulator CpxAR in the virulence of Salmonella enterica serotype Typhimurium.
The CpxAR (Cpx) two-component regulator controls the expression of genes in response to a variety of environmental cues. The Cpx regulator has been implicated in the virulence of several gram-negative pathogens, although a role for Cpx in vivo has not been demonstrated directly. Here we investigate whether positive or negative control of gene expression by Cpx is important for the pathogenesis of Salmonella enterica serotype Typhimurium. The Cpx signal pathway in serotype Typhimurium was disrupted by insertional inactivation of the cpxA and cpxR genes. We also constitutively activated the Cpx pathway by making an internal in-frame deletion in cpxA (a cpxA* mutation). Activation of the Cpx pathway inhibited induction of the envelope stress response pathway controlled by the alternative sigma factor sigma(E) (encoded by rpoE). Conversely, the Cpx pathway was highly up-regulated (>40-fold) in a serotype Typhimurium rpoE mutant. The cpxA* mutation, but not the cpxA or the cpxR mutation, significantly reduced the capacity of serotype Typhimurium to adhere to and invade eucaryotic cells, although intracellular replication was not affected. The cpxA and cpxA* mutations significantly impaired the ability of serotype Typhimurium to grow in vivo in mice. To our knowledge, this is the first demonstration that the Cpx system is important for a bacterial pathogen in vivo.
Molecualr Bacteriology Group, Institute of Comparative Medicine, Department of Veterinary Pathology, Glasgow University Veterinary School, Glasgow G61 1QH, United Kingdom.
Sue
S
Humphreys
Gary
G
Rowley
Andrew
A
Stevenson
Muna F
MF
Anjum
Martin J
MJ
Woodward
Stephen
S
Gilbert
Jan
J
Kormanec
Mark
M
Roberts
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000503:physiopathology; D012486:Salmonella typhimurium / Q000145:classification / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D012703:Serotyping; D015398:Signal Transduction; D014774:Virulence
D001426:Bacterial Proteins; C085504:CpxR protein, Bacteria; D011494:Protein Kinases; C092472:CpxA protein, bacteria