Salmonella pathogenicity island 2 is expressed prior to penetrating the intestine.
Salmonella enterica serovar Typhimurium is a facultative intracellular pathogen that causes disease in mice that resembles human typhoid. Typhoid pathogenesis consists of distinct phases in the intestine and a subsequent systemic phase in which bacteria replicate in macrophages of the liver and spleen. The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI-2) is a major virulence factor contributing to the systemic phase of typhoid pathogenesis. Understanding how pathogens regulate virulence mechanisms in response to the environment, including different host tissues, is key to our understanding of pathogenesis. A recombinase-based in vivo expression technology system was developed to assess SPI-2 expression during murine typhoid. SPI-2 expression was detectable at very early times in bacteria that were resident in the lumen of the ileum and was independent of active bacterial invasion of the epithelium. We also provide direct evidence for the regulation of SPI-2 by the Salmonella transcription factors ompR and ssrB in vivo. Together these results demonstrate that SPI-2 expression precedes penetration of the intestinal epithelium. This induction of expression precedes any documented SPI-2-dependent phases of typhoid and may be involved in preparing Salmonella to successfully resist the antimicrobial environment encountered within macrophages.
Brown
Nat F
NF
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
Vallance
Bruce A
BA
Coombes
Brian K
BK
Valdez
Yanet
Y
Coburn
Bryan A
BA
Finlay
B Brett
BB
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000382:microbiology*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D045522:Recombinases / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D015398:Signal Transduction / Q000235:genetics*; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D008565:Membrane Proteins; D045522:Recombinases; C440638:SPI-2 protein, Salmonella