Home LiteratureArticle Details
PMID: 8633040 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Macrophage killing is an essential virulence mechanism of Salmonella typhimurium.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 9 ·1996-04-30 ·Pages 4197-201

Lindgren SW, Stojiljkovic I, Heffron F

Abstract

Phagocytic cells are a critical line of defense against infection. The ability of a pathogen to survive and even replicate within phagocytic cells is a potent method of evading the defense mechanisms of the host. A number of pathogens survive within macrophages after phagocytosis and this contributes to their virulence. Salmonella is one of these pathogens. Here we report that 6-14 hr after Salmonella enters the macrophage and replicates, it resides in large vacuoles and causes the destruction of these cells. Furthermore, we identified four independently isolated MudJ-lacZ insertion mutants that no longer cause the formation of these vacuoles or kill the macrophages. All four insertions were located in the ompR/envZ regulon. These findings suggest that killing and escape from macrophages may be as important steps in Salmonella pathogenesis as are survival and replication in these host cells.

MeSH Terms
Animals Bacterial Outer Membrane Proteins/biosynthesis Cell Line Cell Survival Cloning, Molecular Escherichia coli Proteins Genetic Complementation Test Macrophages/microbiology,physiology Microscopy, Electron Multienzyme Complexes Mutagenesis, Insertional Operon Recombinant Fusion Proteins/biosynthesis Salmonella typhimurium/genetics,growth & development,pathogenicity Time Factors Transfection Vacuoles/microbiology,physiology Virulence beta-Galactosidase/biosynthesis
Chemicals
Bacterial Outer Membrane Proteins Escherichia coli Proteins Multienzyme Complexes Recombinant Fusion Proteins envZ protein, E coli beta-Galactosidase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lindgren S W
Department of Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.
Stojiljkovic I
Heffron F
References (31)
31 references, click to expand
  1. Transduction with integration-defective mutants of Salmonella typhimurium bacteriophage KB1.
    J Bacteriol. 1974 Feb;117(2):907-8 PMID: 4590490
  2. The lpf fimbrial operon mediates adhesion of Salmonella typhimurium to murine Peyer's patches.
    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):279-83 PMID: 8552622
  3. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent.
    Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189-93 PMID: 3523484
  4. Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study.
    Microbiol Immunol. 1986;30(12):1225-37 PMID: 3553868
  5. OmpR and EnvZ are pleiotropic regulatory proteins: positive regulation of the tripeptide permease (tppB) of Salmonella typhimurium.
    Mol Gen Genet. 1987 Apr;207(1):120-9 PMID: 3037276
  6. Transitory cis complementation: a method for providing transposition functions to defective transposons.
    Genetics. 1988 May;119(1):9-12 PMID: 2840333
  7. Structure and expression of the ompB operon, the regulatory locus for the outer membrane porin regulon in Salmonella typhimurium LT-2.
    J Mol Biol. 1988 Jun 20;201(4):663-73 PMID: 2845093
  8. Characterization of porin and ompR mutants of a virulent strain of Salmonella typhimurium: ompR mutants are attenuated in vivo.
    Infect Immun. 1989 Jul;57(7):2136-40 PMID: 2543631
  9. Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells.
    Proc Natl Acad Sci U S A. 1989 Aug;86(16):6383-7 PMID: 2548211
  10. Invasion and replication of Salmonella typhimurium in animal cells.
    Infect Immun. 1990 Feb;58(2):443-8 PMID: 2404872
  11. The two-component regulatory system ompR-envZ controls the virulence of Shigella flexneri.
    J Bacteriol. 1990 Nov;172(11):6274-81 PMID: 2121709
  12. Salmonella interactions with polarized human intestinal Caco-2 epithelial cells.
    J Infect Dis. 1990 Nov;162(5):1096-106 PMID: 2230236
  13. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  14. Role of ompR-dependent genes in Salmonella typhimurium virulence: mutants deficient in both ompC and ompF are attenuated in vivo.
    Infect Immun. 1991 Jan;59(1):449-52 PMID: 1846127
  15. Construction of versatile low-copy-number vectors for cloning, sequencing and gene expression in Escherichia coli.
    Gene. 1991 Apr;100:195-9 PMID: 2055470
  16. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
    J Cell Biol. 1992 Nov;119(3):493-501 PMID: 1400587
  17. Morphological and cytoskeletal changes in epithelial cells occur immediately upon interaction with Salmonella typhimurium grown under low-oxygen conditions.
    Mol Microbiol. 1992 Nov;6(21):3077-87 PMID: 1360615
  18. Signal transduction and invasion of epithelial cells by S. typhimurium.
    Cell. 1993 Feb 26;72(4):505-14 PMID: 8382566
  19. A cytolysin encoded by Salmonella is required for survival within macrophages.
    Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):489-93 PMID: 8290552
  20. Salmonella stimulate macrophage macropinocytosis and persist within spacious phagosomes.
    J Exp Med. 1994 Feb 1;179(2):601-8 PMID: 8294870
  21. Salmonella typhimurium loci involved in survival within macrophages.
    Infect Immun. 1994 May;62(5):1623-30 PMID: 8168923
  22. IpaB mediates macrophage apoptosis induced by Shigella flexneri.
    Mol Microbiol. 1994 Feb;11(4):619-27 PMID: 8196540
  23. M cells--entryways of opportunity for enteropathogens.
    J Exp Med. 1994 Jul 1;180(1):7-9 PMID: 8006602
  24. Molecular characterization of an enterotoxin from Salmonella typhimurium.
    Microb Pathog. 1994 Feb;16(2):85-98 PMID: 8047004
  25. Characterization of defined ompR mutants of Salmonella typhi: ompR is involved in the regulation of Vi polysaccharide expression.
    Infect Immun. 1994 Sep;62(9):3984-93 PMID: 8063417
  26. Signal transduction by the EnvZ-OmpR phosphotransfer system in bacteria.
    Res Microbiol. 1994 Jun-Aug;145(5-6):363-73 PMID: 7855421
  27. Genetic map of Salmonella typhimurium, edition VIII.
    Microbiol Rev. 1995 Jun;59(2):241-303 PMID: 7603411
  28. Homologs of the Shigella IpaB and IpaC invasins are required for Salmonella typhimurium entry into cultured epithelial cells.
    J Bacteriol. 1995 Jul;177(14):3965-71 PMID: 7608068
  29. Anatomical methods in cell death.
    Methods Cell Biol. 1995;46:1-27 PMID: 7609651
  30. Fur regulon of Salmonella typhimurium: identification of new iron-regulated genes.
    J Bacteriol. 1995 Aug;177(16):4628-37 PMID: 7642488
  31. The ompB locus and the regulation of the major outer membrane porin proteins of Escherichia coli K12.
    J Mol Biol. 1981 Feb 15;146(1):23-43 PMID: 7021856
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.9.4197
Published
1996-04-30
Pages
4197-201
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC39511
Subset
IM
Grants
NIAID NIH HHS · R0I AI 22933 · United States
External Links
PubMed source DOI: 10.1073/pnas.93.9.4197 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2