Skip to main content
NCBI home page
Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2000 May 29;355(1397):623–631. doi: 10.1098/rstb.2000.0603

Salmonella interactions with host cells: in vitro to in vivo.

B B Finlay 1, J H Brumell 1
PMCID: PMC1692772  PMID: 10874735

Abstract

Salmonellosis (diseases caused by Salmonella species) have several clinical manifestations, ranging from gastroenteritis (food poisoning) to typhoid (enteric) fever and bacteraemia. Salmonella species (especially Salmonella typhimurium) also represent organisms that can be readily used to investigate the complex interplay that occurs between a pathogen and its host, both in vitro and in vivo. The ease with which S. typhimurium can be cultivated and genetically manipulated, in combination with the availability of tissue culture models and animal models, has made S. typhimurium a desirable organism for such studies. In this review, we focus on Salmonella interactions with its host cells, both in tissue culture (in vitro) and in relevant animal models (in vivo), and compare results obtained using these different models. The recent advent of sophisticated imaging and molecular genetic tools has facilitated studying the events that occur in disease, thereby confirming tissue culture results, yet identifying new questions that need to be addressed in relevant disease settings.

Full Text

The Full Text of this article is available as a PDF (546.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bowe F., Lipps C. J., Tsolis R. M., Groisman E., Heffron F., Kusters J. G. At least four percent of the Salmonella typhimurium genome is required for fatal infection of mice. Infect Immun. 1998 Jul;66(7):3372–3377. doi: 10.1128/iai.66.7.3372-3377.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brumell J. H., Steele-Mortimer O., Finlay B. B. Bacterial invasion: Force feeding by Salmonella. Curr Biol. 1999 Apr 22;9(8):R277–R280. doi: 10.1016/s0960-9822(99)80178-x. [DOI] [PubMed] [Google Scholar]
  3. Buchmeier N. A., Lipps C. J., So M. Y., Heffron F. Recombination-deficient mutants of Salmonella typhimurium are avirulent and sensitive to the oxidative burst of macrophages. Mol Microbiol. 1993 Mar;7(6):933–936. doi: 10.1111/j.1365-2958.1993.tb01184.x. [DOI] [PubMed] [Google Scholar]
  4. Bäumler A. J., Tsolis R. M., Heffron F. 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):279–283. doi: 10.1073/pnas.93.1.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen L. M., Kaniga K., Galán J. E. Salmonella spp. are cytotoxic for cultured macrophages. Mol Microbiol. 1996 Sep;21(5):1101–1115. doi: 10.1046/j.1365-2958.1996.471410.x. [DOI] [PubMed] [Google Scholar]
  6. Cirillo D. M., Valdivia R. H., Monack D. M., Falkow S. Macrophage-dependent induction of the Salmonella pathogenicity island 2 type III secretion system and its role in intracellular survival. Mol Microbiol. 1998 Oct;30(1):175–188. doi: 10.1046/j.1365-2958.1998.01048.x. [DOI] [PubMed] [Google Scholar]
  7. Collazo C. M., Galán J. E. The invasion-associated type-III protein secretion system in Salmonella--a review. Gene. 1997 Jun 11;192(1):51–59. doi: 10.1016/s0378-1119(96)00825-6. [DOI] [PubMed] [Google Scholar]
  8. Everest P., Ketley J., Hardy S., Douce G., Khan S., Shea J., Holden D., Maskell D., Dougan G. Evaluation of Salmonella typhimurium mutants in a model of experimental gastroenteritis. Infect Immun. 1999 Jun;67(6):2815–2821. doi: 10.1128/iai.67.6.2815-2821.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fang F. C., DeGroote M. A., Foster J. W., Bäumler A. J., Ochsner U., Testerman T., Bearson S., Giárd J. C., Xu Y., Campbell G. Virulent Salmonella typhimurium has two periplasmic Cu, Zn-superoxide dismutases. Proc Natl Acad Sci U S A. 1999 Jun 22;96(13):7502–7507. doi: 10.1073/pnas.96.13.7502. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fields P. I., Swanson R. V., Haidaris C. G., Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5189–5193. doi: 10.1073/pnas.83.14.5189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Finlay B. B., Ruschkowski S., Dedhar S. Cytoskeletal rearrangements accompanying salmonella entry into epithelial cells. J Cell Sci. 1991 Jun;99(Pt 2):283–296. doi: 10.1242/jcs.99.2.283. [DOI] [PubMed] [Google Scholar]
  12. Fu Y., Galán J. E. A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature. 1999 Sep 16;401(6750):293–297. doi: 10.1038/45829. [DOI] [PubMed] [Google Scholar]
  13. Fu Y., Galán J. E. The Salmonella typhimurium tyrosine phosphatase SptP is translocated into host cells and disrupts the actin cytoskeleton. Mol Microbiol. 1998 Jan;27(2):359–368. doi: 10.1046/j.1365-2958.1998.00684.x. [DOI] [PubMed] [Google Scholar]
  14. Galyov E. E., Wood M. W., Rosqvist R., Mullan P. B., Watson P. R., Hedges S., Wallis T. S. A secreted effector protein of Salmonella dublin is translocated into eukaryotic cells and mediates inflammation and fluid secretion in infected ileal mucosa. Mol Microbiol. 1997 Sep;25(5):903–912. doi: 10.1111/j.1365-2958.1997.mmi525.x. [DOI] [PubMed] [Google Scholar]
  15. Galán J. E., Curtiss R., 3rd 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):6383–6387. doi: 10.1073/pnas.86.16.6383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Garcia-del Portillo F., Finlay B. B. Salmonella invasion of nonphagocytic cells induces formation of macropinosomes in the host cell. Infect Immun. 1994 Oct;62(10):4641–4645. doi: 10.1128/iai.62.10.4641-4645.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Garcia-del Portillo F., Finlay B. B. Targeting of Salmonella typhimurium to vesicles containing lysosomal membrane glycoproteins bypasses compartments with mannose 6-phosphate receptors. J Cell Biol. 1995 Apr;129(1):81–97. doi: 10.1083/jcb.129.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gewirtz A. T., Siber A. M., Madara J. L., McCormick B. A. Orchestration of neutrophil movement by intestinal epithelial cells in response to Salmonella typhimurium can be uncoupled from bacterial internalization. Infect Immun. 1999 Feb;67(2):608–617. doi: 10.1128/iai.67.2.608-617.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Groisman E. A., Ochman H. How Salmonella became a pathogen. Trends Microbiol. 1997 Sep;5(9):343–349. doi: 10.1016/S0966-842X(97)01099-8. [DOI] [PubMed] [Google Scholar]
  20. Hardt W. D., Chen L. M., Schuebel K. E., Bustelo X. R., Galán J. E. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell. 1998 May 29;93(5):815–826. doi: 10.1016/s0092-8674(00)81442-7. [DOI] [PubMed] [Google Scholar]
  21. Hardt W. D., Urlaub H., Galán J. E. A substrate of the centisome 63 type III protein secretion system of Salmonella typhimurium is encoded by a cryptic bacteriophage. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2574–2579. doi: 10.1073/pnas.95.5.2574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hayward R. D., Koronakis V. Direct nucleation and bundling of actin by the SipC protein of invasive Salmonella. EMBO J. 1999 Sep 15;18(18):4926–4934. doi: 10.1093/emboj/18.18.4926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hensel M., Shea J. E., Waterman S. R., Mundy R., Nikolaus T., Banks G., Vazquez-Torres A., Gleeson C., Fang F. C., Holden D. W. Genes encoding putative effector proteins of the type III secretion system of Salmonella pathogenicity island 2 are required for bacterial virulence and proliferation in macrophages. Mol Microbiol. 1998 Oct;30(1):163–174. doi: 10.1046/j.1365-2958.1998.01047.x. [DOI] [PubMed] [Google Scholar]
  24. Hersh D., Monack D. M., Smith M. R., Ghori N., Falkow S., Zychlinsky A. The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2396–2401. doi: 10.1073/pnas.96.5.2396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hoiseth S. K., Stocker B. A. Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature. 1981 May 21;291(5812):238–239. doi: 10.1038/291238a0. [DOI] [PubMed] [Google Scholar]
  26. Hong K. H., Miller V. L. Identification of a novel Salmonella invasion locus homologous to Shigella ipgDE. J Bacteriol. 1998 Apr;180(7):1793–1802. doi: 10.1128/jb.180.7.1793-1802.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Jones B. D., Falkow S. Salmonellosis: host immune responses and bacterial virulence determinants. Annu Rev Immunol. 1996;14:533–561. doi: 10.1146/annurev.immunol.14.1.533. [DOI] [PubMed] [Google Scholar]
  28. Jones B. D., Ghori N., Falkow S. Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches. J Exp Med. 1994 Jul 1;180(1):15–23. doi: 10.1084/jem.180.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kim J. M., Eckmann L., Savidge T. C., Lowe D. C., Witthöft T., Kagnoff M. F. Apoptosis of human intestinal epithelial cells after bacterial invasion. J Clin Invest. 1998 Nov 15;102(10):1815–1823. doi: 10.1172/JCI2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lalmanach A. C., Lantier F. Host cytokine response and resistance to Salmonella infection. Microbes Infect. 1999 Jul;1(9):719–726. doi: 10.1016/s1286-4579(99)80073-2. [DOI] [PubMed] [Google Scholar]
  31. Lundberg B. E., Wolf R. E., Jr, Dinauer M. C., Xu Y., Fang F. C. Glucose 6-phosphate dehydrogenase is required for Salmonella typhimurium virulence and resistance to reactive oxygen and nitrogen intermediates. Infect Immun. 1999 Jan;67(1):436–438. doi: 10.1128/iai.67.1.436-438.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. McCormick B. A., Colgan S. P., Delp-Archer C., Miller S. I., Madara J. L. Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. J Cell Biol. 1993 Nov;123(4):895–907. doi: 10.1083/jcb.123.4.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. McCormick B. A., Miller S. I., Carnes D., Madara J. L. Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis. Infect Immun. 1995 Jun;63(6):2302–2309. doi: 10.1128/iai.63.6.2302-2309.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. McCormick B. A., Parkos C. A., Colgan S. P., Carnes D. K., Madara J. L. Apical secretion of a pathogen-elicited epithelial chemoattractant activity in response to surface colonization of intestinal epithelia by Salmonella typhimurium. J Immunol. 1998 Jan 1;160(1):455–466. [PubMed] [Google Scholar]
  35. Mills S. D., Finlay B. B. Comparison of Salmonella typhi and Salmonella typhimurium invasion, intracellular growth and localization in cultured human epithelial cells. Microb Pathog. 1994 Dec;17(6):409–423. doi: 10.1006/mpat.1994.1086. [DOI] [PubMed] [Google Scholar]
  36. Mills S. D., Finlay B. B. Isolation and characterization of Salmonella typhimurium and Yersinia pseudotuberculosis-containing phagosomes from infected mouse macrophages: Y. pseudotuberculosis traffics to terminal lysosomes where they are degraded. Eur J Cell Biol. 1998 Sep;77(1):35–47. doi: 10.1016/S0171-9335(98)80100-3. [DOI] [PubMed] [Google Scholar]
  37. Monack D. M., Raupach B., Hromockyj A. E., Falkow S. Salmonella typhimurium invasion induces apoptosis in infected macrophages. Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9833–9838. doi: 10.1073/pnas.93.18.9833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Méresse S., Steele-Mortimer O., Finlay B. B., Gorvel J. P. The rab7 GTPase controls the maturation of Salmonella typhimurium-containing vacuoles in HeLa cells. EMBO J. 1999 Aug 16;18(16):4394–4403. doi: 10.1093/emboj/18.16.4394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ochman H., Soncini F. C., Solomon F., Groisman E. A. Identification of a pathogenicity island required for Salmonella survival in host cells. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7800–7804. doi: 10.1073/pnas.93.15.7800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Pier G. B., Grout M., Zaidi T., Meluleni G., Mueschenborn S. S., Banting G., Ratcliff R., Evans M. J., Colledge W. H. Salmonella typhi uses CFTR to enter intestinal epithelial cells. Nature. 1998 May 7;393(6680):79–82. doi: 10.1038/30006. [DOI] [PubMed] [Google Scholar]
  41. Rathman M., Barker L. P., Falkow S. The unique trafficking pattern of Salmonella typhimurium-containing phagosomes in murine macrophages is independent of the mechanism of bacterial entry. Infect Immun. 1997 Apr;65(4):1475–1485. doi: 10.1128/iai.65.4.1475-1485.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Richter-Dahlfors A., Buchan A. M., Finlay B. B. Murine salmonellosis studied by confocal microscopy: Salmonella typhimurium resides intracellularly inside macrophages and exerts a cytotoxic effect on phagocytes in vivo. J Exp Med. 1997 Aug 18;186(4):569–580. doi: 10.1084/jem.186.4.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Salama N. R., Falkow S. Genomic clues for defining bacterial pathogenicity. Microbes Infect. 1999 Jul;1(8):615–619. doi: 10.1016/s1286-4579(99)80061-6. [DOI] [PubMed] [Google Scholar]
  44. Shea J. E., Hensel M., Gleeson C., Holden D. W. Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2593–2597. doi: 10.1073/pnas.93.6.2593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Steele-Mortimer O., Méresse S., Gorvel J. P., Toh B. H., Finlay B. B. Biogenesis of Salmonella typhimurium-containing vacuoles in epithelial cells involves interactions with the early endocytic pathway. Cell Microbiol. 1999 Jul;1(1):33–49. doi: 10.1046/j.1462-5822.1999.00003.x. [DOI] [PubMed] [Google Scholar]
  46. Takeuchi A. Electron microscope studies of experimental Salmonella infection. I. Penetration into the intestinal epithelium by Salmonella typhimurium. Am J Pathol. 1967 Jan;50(1):109–136. [PMC free article] [PubMed] [Google Scholar]
  47. Uchiya K., Barbieri M. A., Funato K., Shah A. H., Stahl P. D., Groisman E. A. A Salmonella virulence protein that inhibits cellular trafficking. EMBO J. 1999 Jul 15;18(14):3924–3933. doi: 10.1093/emboj/18.14.3924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Wood M. W., Jones M. A., Watson P. R., Hedges S., Wallis T. S., Galyov E. E. Identification of a pathogenicity island required for Salmonella enteropathogenicity. Mol Microbiol. 1998 Aug;29(3):883–891. doi: 10.1046/j.1365-2958.1998.00984.x. [DOI] [PubMed] [Google Scholar]
  49. Zhou D., Mooseker M. S., Galán J. E. An invasion-associated Salmonella protein modulates the actin-bundling activity of plastin. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10176–10181. doi: 10.1073/pnas.96.18.10176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Zhou D., Mooseker M. S., Galán J. E. Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. Science. 1999 Mar 26;283(5410):2092–2095. doi: 10.1126/science.283.5410.2092. [DOI] [PubMed] [Google Scholar]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES