Type III secretion chaperone-dependent regulation: activation of virulence genes by SicA and InvF in Salmonella typhimurium.
Invasion of the intestinal epithelium by Salmonella sp. requires a type III secretion system (TTSS) common in many bacterial pathogens. TTSS translocate effector proteins from bacteria into eukaryotic cells. These effectors manipulate cellular functions in order to benefit the pathogen. In the human and animal pathogen Salmonella typhimurium, the expression of genes encoding the secreted effector molecules Sip/Ssp ABCD, SigD, SptP and SopE requires both the AraC/XylS-like regulator InvF and the secretion chaperone SICA: In this work, an InvF binding site was identified in the promoter regions of three operons. SicA does not appear to affect InvF stability nor to bind DNA directly. However, SicA could be co-purified with InvF, suggesting that InvF and SicA interact with each other to activate transcription from the effector gene promoters. This is the first demonstration of a contact between a protein cofactor and an AraC/XylS family transcriptional regulator and, moreover, is the first direct evidence of an interaction between a transcriptional regulator and a TTSS chaperone. The regulation of effector genes described here for InvF and SicA may represent a new paradigm for regulation of virulence in a wide variety of pathogens.
Darwin
K H
KH
Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA.
Miller
V L
VL
D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000235:genetics; D005408:Flagellin / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012329:RNA, Bacterial / Q000378:metabolism; D018085:Regulon / Q000235:genetics; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D017384:Sequence Deletion; D014157:Transcription Factors
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D012329:RNA, Bacterial; C094577:SicA protein, Salmonella typhimurium; C103987:SopE protein, Salmonella; D014157:Transcription Factors; C090990:invF protein, Salmonella; D005408:Flagellin; C416532:flaB flagellin