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PMID: 8392513 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

A PhoP-repressed gene promotes Salmonella typhimurium invasion of epithelial cells.

Journal of bacteriology ·Vol. 175 ·No. 14 ·1993-07-00 ·Pages 4475-84

Behlau I, Miller SI

Abstract

The Salmonella typhimurium transcriptional regulators, PhoP/PhoQ, induce phoP-activated gene (pag) expression to promote virulence and intracellular survival within macrophages. This response to the macrophage intracellular environment is simulated by phoP/phoQ constitutive mutations (phenotype PhoPc) that increase the expression of pag genes and repress the synthesis of approximately 20 proteins encoded by phoP-repressed genes (prg genes) (S. I. Miller and J. J. Mekalanos, J. Bacteriol. 172:2485-2490, 1990). PhoPc bacteria are attenuated for mouse virulence, suggesting that prg genes are virulence genes. We now report the identification of five unlinked prg loci by use of the transposon TnphoA. In general, medium conditions (i.e., starvation) that activate pag expression repress prg expression. However, variable effects on the PhoP regulon were observed when bacteria were grown under different oxygen tensions (pag and prg genes) or exposed to low pH (prg genes), suggesting heterogenous control of the regulon. One prg locus, prgH, was demonstrated to contribute to mouse virulence by both the oral and the intraperitoneal routes. prgH was located at 59 min on the Salmonella chromosome, a region where other genes essential to invasion of epithelial cells are clustered. The prgH locus was highly linked to one invasion locus, hil (C.A. Lee, B.D. Jones, and S. Falkow, Proc. Natl. Acad. Sci. USA 89:1847-1851, 1992), although transcription of prgH was opposite that of the Tn5B50-encoded promoters that result in a hyperinvasive or hil phenotype. Both PrgH and PhoPc mutant S. typhimurium were found to be defective in induction of endocytosis by Madin-Darby canine kidney (MDCK) epithelial cells. The invasion defect of PrgH but not that of PhoPc mutant bacteria was complemented by plasmids containing prgH (hil) DNA. Therefore, two virulence properties of Salmonella species, induction of endocytosis by epithelial cells and survival within macrophages, are oppositely modulated by the PhoP/PhoQ virulence regulators.

Related Genes
hil pag phoA phoP prg prgH
MeSH Terms
Animals Bacterial Adhesion Bacterial Proteins/metabolism Cell Line Cells, Cultured Chromosome Mapping DNA Transposable Elements Epithelium/microbiology Gene Expression Regulation, Bacterial Genes, Bacterial Genetic Linkage Genotype Macrophages/microbiology Mice Mice, Inbred BALB C Mutagenesis Promoter Regions, Genetic Salmonella typhimurium/genetics,pathogenicity,physiology Transcription Factors/metabolism Virulence/genetics
Chemicals
Bacterial Proteins DNA Transposable Elements Transcription Factors PhoP protein, Bacteria
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Behlau I
Infectious Disease Unit, Massachusetts General Hospital, Boston.
Miller S I
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Article Info
Journal
Journal of bacteriology
Abbr.
J Bacteriol
ISSN
0021-9193
DOI
10.1128/jb.175.14.4475-4484.1993
Published
1993-07-00
Pages
4475-84
Language
English
Region
United States
NLM ID
2985120R
PMCID
PMC204888
Subset
IM
Grants
NIAID NIH HHS · AI00917 · United States
NIAID NIH HHS · AI08280 · United States
NIAID NIH HHS · AI30479 · United States
External Links
PubMed source DOI: 10.1128/jb.175.14.4475-4484.1993 PMC Full Text View journal details
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