A rapid change in virulence gene expression during the transition from the intestinal lumen into tissue promotes systemic dissemination of Salmonella.
Bacterial pathogens causing systemic disease commonly evolve from organisms associated with localized infections but differ from their close relatives in their ability to overcome mucosal barriers by mechanisms that remain incompletely understood. Here we investigated whether acquisition of a regulatory gene, tviA, contributed to the ability of Salmonella enterica serotype Typhi to disseminate from the intestine to systemic sites of infection during typhoid fever. To study the consequences of acquiring a new regulator by horizontal gene transfer, tviA was introduced into the chromosome of S. enterica serotype Typhimurium, a closely related pathogen causing a localized gastrointestinal infection in immunocompetent individuals. TviA repressed expression of flagellin, a pathogen associated molecular pattern (PAMP), when bacteria were grown at osmotic conditions encountered in tissue, but not at higher osmolarity present in the intestinal lumen. TviA-mediated flagellin repression enabled bacteria to evade sentinel functions of human model epithelia and resulted in increased bacterial dissemination to the spleen in a chicken model. Collectively, our data point to PAMP repression as a novel pathogenic mechanism to overcome the mucosal barrier through innate immune evasion.
Winter
Sebastian E
SE
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, Davis, California, USA.
Winter
Maria G
MG
Godinez
Ivan
I
Yang
Hee-Jeong
HJ
Rüssmann
Holger
H
Andrews-Polymenis
Helene L
HL
Bäumler
Andreas J
AJ
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D015153:Blotting, Western; D002460:Cell Line; D002645:Chickens; D004591:Electrophoresis, Polyacrylamide Gel; D005408:Flagellin / Q000096:biosynthesis; D005434:Flow Cytometry; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D057131:Immune Evasion; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012475:Salmonella / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D012481:Salmonella Infections, Animal / Q000235:genetics* / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*; D014435:Typhoid Fever / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D014157:Transcription Factors; C098634:tviA protein, Salmonella typhi; D005408:Flagellin
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