Feverlike Temperature is a Virulence Regulatory Cue Controlling the Motility and Host Cell Entry of Typhoidal Salmonella

J Infect Dis. 2015 Jul 1;212(1):147-56. doi: 10.1093/infdis/jiu663. Epub 2014 Dec 9.


Human infection with typhoidal Salmonella serovars causes a febrile systemic disease, termed enteric fever. Here we establish that in response to a temperature equivalent to fever (39 °C-42 °C) Salmonella enterica serovars Typhi, Paratyphi A, and Sendai significantly attenuate their motility, epithelial cell invasion, and uptake by macrophages. Under these feverlike conditions, the residual epithelial cell invasion of S. Paratyphi A occurs in a type III secretion system (T3SS) 1-independent manner and results in restrained disruption of epithelium integrity. The impaired motility and invasion are associated with down-regulation of T3SS-1 genes and class II and III (but not I) of the flagella-chemotaxis regulon. In contrast, we demonstrate up-regulation of particular Salmonella pathogenicity island 2 genes (especially spiC) and increased intraepithelial growth in a T3SS-2-dependent manner. These results indicate that elevated physiological temperature is a novel cue controlling virulence phenotypes in typhoidal serovars, which is likely to play a role in the distinct clinical manifestations elicited by typhoidal and nontyphoidal salmonellae.

Keywords: Salmonella; enteric fever; flagella; invasion; motility; paratyphoid; pathogenicity; pyrexia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Line
  • Endocytosis / radiation effects*
  • Epithelial Cells / microbiology
  • Epithelial Cells / radiation effects
  • Fever*
  • Gene Expression Regulation, Bacterial / radiation effects*
  • Humans
  • Locomotion / radiation effects*
  • Macrophages / microbiology
  • Macrophages / radiation effects
  • Salmonella enterica / genetics
  • Salmonella enterica / physiology*
  • Salmonella enterica / radiation effects*
  • Temperature
  • Virulence / radiation effects
  • Virulence Factors / metabolism*


  • Virulence Factors