The Role of the Spv Genes in Salmonella Pathogenesis

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2011 Jul 1

PMID 21716657

Citations 109

Authors

Donald G Guiney

Joshua Fierer

Affiliations

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Abstract

Salmonella strains cause three main types of diseases in people: gastroenteritis, enteric (typhoid) fever, and non-typhoid extra-intestinal disease with bacteremia. Genetic analysis indicates that each clinical syndrome requires distinct sets of virulence genes, and Salmonella isolates differ in their constellation of virulence traits. The spv locus is strongly associated with strains that cause non-typhoid bacteremia, but are not present in typhoid strains. The spv region contains three genes required for the virulence phenotype in mice: the positive transcriptional regulator spvR and two structural genes spvB and spvC. SpvB and SpvC are translocated into the host cell by the Salmonella pathogenicity island-2 type-three secretion system. SpvB prevents actin polymerization by ADP-ribosylation of actin monomers, while SpvC has phosphothreonine lyase activity and has been shown to inhibit MAP kinase signaling. The exact mechanisms by which SpvB and SpvC act in concert to enhance virulence are still unclear. SpvB exhibits a cytotoxic effect on host cells and is required for delayed cell death by apoptosis following intracellular infection. Strains isolated from systemic infections of immune compromised patients, particularly HIV patients, usually carry the spv locus, strongly suggesting that CD4 T cells are required to control disease due to Salmonella that are spv positive. This association is not seen with typhoid fever, indicating that the pathogenesis and immunology of typhoid have fundamental differences from the syndrome of non-typhoid bacteremia.

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References

Fierer J, Guiney D . Diverse virulence traits underlying different clinical outcomes of Salmonella infection. J Clin Invest. 2001; 107(7):775-80. PMC: 199580. DOI: 10.1172/JCI12561. View

Cohen P, OBrien T, Schoenbaum S, Medeiros A . The risk of endothelial infection in adults with salmonella bacteremia. Ann Intern Med. 1978; 89(6):931-2. DOI: 10.7326/0003-4819-89-6-931. View

MacCREADY R, REARDON J, SAPHRA I . Salmonellosis in Massachusetts; a sixteen-year experience. N Engl J Med. 1957; 256(24):1121-8. DOI: 10.1056/NEJM195706132562401. View

Raupach B, Peuschel S, Monack D, Zychlinsky A . Caspase-1-mediated activation of interleukin-1beta (IL-1beta) and IL-18 contributes to innate immune defenses against Salmonella enterica serovar Typhimurium infection. Infect Immun. 2006; 74(8):4922-6. PMC: 1539628. DOI: 10.1128/IAI.00417-06. View

Krause M, Fang F, Guiney D . Regulation of plasmid virulence gene expression in Salmonella dublin involves an unusual operon structure. J Bacteriol. 1992; 174(13):4482-9. PMC: 206235. DOI: 10.1128/jb.174.13.4482-4489.1992. View

Arthur G, Nduba V, Kariuki S, Kimari J, Bhatt S, Gilks C . Trends in bloodstream infections among human immunodeficiency virus-infected adults admitted to a hospital in Nairobi, Kenya, during the last decade. Clin Infect Dis. 2001; 33(2):248-56. DOI: 10.1086/321820. View

Tauxe R . Emerging foodborne diseases: an evolving public health challenge. Emerg Infect Dis. 1997; 3(4):425-34. PMC: 2640074. DOI: 10.3201/eid0304.970403. View

Vassiloyanakopoulos A, Okamoto S, Fierer J . The crucial role of polymorphonuclear leukocytes in resistance to Salmonella dublin infections in genetically susceptible and resistant mice. Proc Natl Acad Sci U S A. 1998; 95(13):7676-81. PMC: 22720. DOI: 10.1073/pnas.95.13.7676. View

SAPHRA I, Winter J . Clinical manifestations of salmonellosis in man; an evaluation of 7779 human infections identified at the New York Salmonella Center. N Engl J Med. 1957; 256(24):1128-34. DOI: 10.1056/NEJM195706132562402. View

10.

Paesold G, Guiney D, Eckmann L, Kagnoff M . Genes in the Salmonella pathogenicity island 2 and the Salmonella virulence plasmid are essential for Salmonella-induced apoptosis in intestinal epithelial cells. Cell Microbiol. 2002; 4(11):771-81. DOI: 10.1046/j.1462-5822.2002.00233.x. View

11.

Hsu L, Park J, Zhang K, Luo J, Maeda S, Kaufman R . The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature. 2004; 428(6980):341-5. DOI: 10.1038/nature02405. View

12.

Guiney D, Lesnick M . Targeting of the actin cytoskeleton during infection by Salmonella strains. Clin Immunol. 2005; 114(3):248-55. DOI: 10.1016/j.clim.2004.07.014. View

13.

Galan J . Salmonella interactions with host cells: type III secretion at work. Annu Rev Cell Dev Biol. 2001; 17:53-86. DOI: 10.1146/annurev.cellbio.17.1.53. View

14.

Jones T, Ingram L, Cieslak P, Vugia D, Tobin-DAngelo M, Hurd S . Salmonellosis outcomes differ substantially by serotype. J Infect Dis. 2008; 198(1):109-14. DOI: 10.1086/588823. View

15.

Abrahams G, Muller P, Hensel M . Functional dissection of SseF, a type III effector protein involved in positioning the salmonella-containing vacuole. Traffic. 2006; 7(8):950-65. DOI: 10.1111/j.1600-0854.2006.00454.x. View

16.

Gallois A, Klein J, Allen L, Jones B, Nauseef W . Salmonella pathogenicity island 2-encoded type III secretion system mediates exclusion of NADPH oxidase assembly from the phagosomal membrane. J Immunol. 2001; 166(9):5741-8. DOI: 10.4049/jimmunol.166.9.5741. View

17.

Fink S, Cookson B . Pyroptosis and host cell death responses during Salmonella infection. Cell Microbiol. 2007; 9(11):2562-70. DOI: 10.1111/j.1462-5822.2007.01036.x. View

18.

Lara-Tejero M, Sutterwala F, Ogura Y, Grant E, Bertin J, Coyle A . Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J Exp Med. 2006; 203(6):1407-12. PMC: 2118315. DOI: 10.1084/jem.20060206. View

19.

Kingsley R, Msefula C, Thomson N, Kariuki S, Holt K, Gordon M . Epidemic multiple drug resistant Salmonella Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome Res. 2009; 19(12):2279-87. PMC: 2792184. DOI: 10.1101/gr.091017.109. View

20.

Mendelowitz D, Ramstedt R, Yao J, Bergan J . Abdominal aortic salmonellosis. Surgery. 1979; 85(5):514-9. View