title: Feverlike Temperature is a Virulence Regulatory Cue Controlling the Motility and Host Cell Entry of Typhoidal Salmonella.
abstract: 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.
authors.affiliation: The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer The Department of Clinical Microbiology and Immunology Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Elhadad
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Irvine.
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
authors.affiliation: The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Galia
authors.initials: G
authors.lastname: Rahav
authors.affiliation: The Infectious Diseases Research Laboratory, Sheba Medical Center, Tel-Hashomer The Department of Clinical Microbiology and Immunology Sackler School of Medicine, Tel Aviv University, Israel.
authors.forename: Ohad
authors.initials: O
authors.lastname: Gal-Mor
mesh_terms: D002460:Cell Line; D004705:Endocytosis / Q000528:radiation effects*; D004847:Epithelial Cells / Q000382:microbiology / Q000528:radiation effects; D005334:Fever; D015964:Gene Expression Regulation, Bacterial / Q000528:radiation effects*; D006801:Humans; D008124:Locomotion / Q000528:radiation effects*; D008264:Macrophages / Q000382:microbiology / Q000528:radiation effects; D019779:Salmonella enterica / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects*; D013696:Temperature; D014774:Virulence / Q000528:radiation effects; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D037521:Virulence Factors
keywords: Salmonella; enteric fever; flagella; invasion; motility; paratyphoid; pathogenicity; pyrexia