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Pathogenesis of Salmonella gastroenteritis

Camille N Kotton, MD
Elizabeth L Hohmann, MD
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Allyson Bloom, MD


Salmonellae cause a broad range of infections, including gastroenteritis, enteric fever, bacteremia, endovascular infections, and focal infections such as osteomyelitis and abscesses. Salmonellae are facultative anaerobic gram-negative bacilli and usually enter the body via the gastrointestinal (GI) tract, where they can persist for long periods of time. Salmonellae can act as both commensals and pathogens and are found in the GI tracts of domestic and wild animals, including insects, reptiles, birds, and mammals.

Although there are many types of Salmonella, they can be divided into two broad categories: those that cause typhoid and enteric fever and those that primarily induce gastroenteritis:

The typhoidal Salmonella, such as Salmonella Typhi or Salmonella Paratyphi primarily colonize humans, are transmitted via the consumption of fecally contaminated food or water, and cause a systemic illness usually with little or no diarrhea. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of enteric (typhoid and paratyphoid) fever".)

The much broader group of nontyphoidal Salmonella usually results from improperly handled food that has been contaminated by animal or human fecal material. It can also be acquired via the fecal-oral route, either from other humans or farm or pet animals [1]. (See "Nontyphoidal Salmonella: Microbiology and epidemiology".)

The bacterial and host factors that contribute to Salmonella gastroenteritis will be reviewed here (figure 1). The approach to patients with Salmonella in a stool culture is discussed separately. (See "Nontyphoidal Salmonella: Gastrointestinal infection and carriage".)

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Literature review current through: Nov 2017. | This topic last updated: Aug 09, 2017.
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  1. Hohmann EL. Nontyphoidal salmonellosis. Clin Infect Dis 2001; 32:263.
  2. Blaser MJ, Feldman RA. From the centers for disease control. Salmonella bacteremia: reports to the Centers for Disease Control, 1968-1979. J Infect Dis 1981; 143:743.
  3. McNabb SJ, Jajosky RA, Hall-Baker PA, et al. Summary of notifiable diseases--United States, 2006. MMWR Morb Mortal Wkly Rep 2008; 55:1.
  4. Mead PS, Slutsker L, Dietz V, et al. Food-related illness and death in the United States. Emerg Infect Dis 1999; 5:607.
  5. Centers for Disease Control and Prevention (CDC). Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food--10 States, United States, 2005. MMWR Morb Mortal Wkly Rep 2006; 55:392.
  6. Hope BK, Baker R, Edel ED, et al. An overview of the Salmonella enteritidis risk assessment for shell eggs and egg products. Risk Anal 2002; 22:203.
  7. Sivapalasingam S, Barrett E, Kimura A, et al. A multistate outbreak of Salmonella enterica Serotype Newport infection linked to mango consumption: impact of water-dip disinfestation technology. Clin Infect Dis 2003; 37:1585.
  8. Centers for Disease Control and Prevention (CDC). Reptile-associated salmonellosis--selected states, 1998-2002. MMWR Morb Mortal Wkly Rep 2003; 52:1206.
  9. Blaser MJ, Newman LS. A review of human salmonellosis: I. Infective dose. Rev Infect Dis 1982; 4:1096.
  10. Agunod M, Yamaguchi N, Lopez R, et al. Correlative study of hydrochloric acid, pepsin, and intrinsic factor secretion in newborns and infants. Am J Dig Dis 1969; 14:400.
  11. Riley LW, Cohen ML, Seals JE, et al. Importance of host factors in human salmonellosis caused by multiresistant strains of Salmonella. J Infect Dis 1984; 149:878.
  12. KUNZ LJ, WADDELL WR. Association of Salmonella enteritis with operations on the stomach. N Engl J Med 1956; 255:555.
  13. Neal KR, Briji SO, Slack RC, et al. Recent treatment with H2 antagonists and antibiotics and gastric surgery as risk factors for Salmonella infection. BMJ 1994; 308:176.
  14. Giannella RA, Broitman SA, Zamcheck N. Gastric acid barrier to ingested microorganisms in man: studies in vivo and in vitro. Gut 1972; 13:251.
  15. Foster JW. Low pH adaptation and the acid tolerance response of Salmonella typhimurium. Crit Rev Microbiol 1995; 21:215.
  17. Que JU, Casey SW, Hentges DJ. Factors responsible for increased susceptibility of mice to intestinal colonization after treatment with streptomycin. Infect Immun 1986; 53:116.
  18. Tannock GW, Savage DC. Indigenous microorganisms prevent reduction in cecal size induced by Salmonella typhimurium in vaccinated gnotobiotic mice. Infect Immun 1976; 13:172.
  19. Mentzing LO, Ringertz O. Salmonella infection in tourists. 2. Prophylaxis against salmonellosis. Acta Pathol Microbiol Scand 1968; 74:405.
  20. Ryan CA, Nickels MK, Hargrett-Bean NT, et al. Massive outbreak of antimicrobial-resistant salmonellosis traced to pasteurized milk. JAMA 1987; 258:3269.
  21. Pavia AT, Shipman LD, Wells JG, et al. Epidemiologic evidence that prior antimicrobial exposure decreases resistance to infection by antimicrobial-sensitive Salmonella. J Infect Dis 1990; 161:255.
  22. Thiennimitr P, Winter SE, Winter MG, et al. Intestinal inflammation allows Salmonella to use ethanolamine to compete with the microbiota. Proc Natl Acad Sci U S A 2011; 108:17480.
  23. Selsted ME, Miller SI, Henschen AH, Ouellette AJ. Enteric defensins: antibiotic peptide components of intestinal host defense. J Cell Biol 1992; 118:929.
  24. Michetti P, Mahan MJ, Slauch JM, et al. Monoclonal secretory immunoglobulin A protects mice against oral challenge with the invasive pathogen Salmonella typhimurium. Infect Immun 1992; 60:1786.
  25. Ledeboer NA, Frye JG, McClelland M, Jones BD. Salmonella enterica serovar Typhimurium requires the Lpf, Pef, and Tafi fimbriae for biofilm formation on HEp-2 tissue culture cells and chicken intestinal epithelium. Infect Immun 2006; 74:3156.
  26. Weening EH, Barker JD, Laarakker MC, et al. The Salmonella enterica serotype Typhimurium lpf, bcf, stb, stc, std, and sth fimbrial operons are required for intestinal persistence in mice. Infect Immun 2005; 73:3358.
  27. Cellular Microbiology, Cossart P, Boquet P, Normark S, Rappuoli R (Eds), ASM Press, Washington, DC 2000.
  28. Kohbata S, Yokoyama H, Yabuuchi E. 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; 30:1225.
  29. Hughes EA, Galán JE. Immune response to Salmonella: location, location, location? Immunity 2002; 16:325.
  30. Pace J, Hayman MJ, Galán JE. Signal transduction and invasion of epithelial cells by S. typhimurium. Cell 1993; 72:505.
  31. Finlay BB, Gumbiner B, Falkow S. Penetration of Salmonella through a polarized Madin-Darby canine kidney epithelial cell monolayer. J Cell Biol 1988; 107:221.
  32. Halle S, Bumann D, Herbrand H, et al. Solitary intestinal lymphoid tissue provides a productive port of entry for Salmonella enterica serovar Typhimurium. Infect Immun 2007; 75:1577.
  33. Steele-Mortimer O. The Salmonella-containing vacuole: moving with the times. Curr Opin Microbiol 2008; 11:38.
  34. Kingsley RA, Humphries AD, Weening EH, et al. Molecular and phenotypic analysis of the CS54 island of Salmonella enterica serotype typhimurium: identification of intestinal colonization and persistence determinants. Infect Immun 2003; 71:629.
  35. Hueck CJ, Hantman MJ, Bajaj V, et al. Salmonella typhimurium secreted invasion determinants are homologous to Shigella Ipa proteins. Mol Microbiol 1995; 18:479.
  36. Galán JE. Molecular genetic bases of Salmonella entry into host cells. Mol Microbiol 1996; 20:263.
  37. Lee CA, Jones BD, Falkow S. Identification of a Salmonella typhimurium invasion locus by selection for hyperinvasive mutants. Proc Natl Acad Sci U S A 1992; 89:1847.
  38. Behlau I, Miller SI. A PhoP-repressed gene promotes Salmonella typhimurium invasion of epithelial cells. J Bacteriol 1993; 175:4475.
  39. Ochman H, Soncini FC, Solomon F, Groisman EA. Identification of a pathogenicity island required for Salmonella survival in host cells. Proc Natl Acad Sci U S A 1996; 93:7800.
  40. Shea JE, Hensel M, Gleeson C, Holden DW. Identification of a virulence locus encoding a second type III secretion system in Salmonella typhimurium. Proc Natl Acad Sci U S A 1996; 93:2593.
  41. Hensel M, Shea JE, Waterman SR, et al. 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; 30:163.
  42. Watson PR, Paulin SM, Bland AP, et al. Characterization of intestinal invasion by Salmonella typhimurium and Salmonella dublin and effect of a mutation in the invH gene. Infect Immun 1995; 63:2743.
  43. Galyov EE, Wood MW, Rosqvist R, et al. 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; 25:903.
  44. Francis CL, Ryan TA, Jones BD, et al. Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria. Nature 1993; 364:639.
  45. Hannemann S, Galán JE. Salmonella enterica serovar-specific transcriptional reprogramming of infected cells. PLoS Pathog 2017; 13:e1006532.
  46. Ginocchio CC, Rahn K, Clarke RC, Galán JE. Naturally occurring deletions in the centisome 63 pathogenicity island of environmental isolates of Salmonella spp. Infect Immun 1997; 65:1267.
  47. McCormick BA, Colgan SP, Delp-Archer C, et al. Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils. J Cell Biol 1993; 123:895.
  48. Tükel C, Raffatellu M, Chessa D, et al. Neutrophil influx during non-typhoidal salmonellosis: who is in the driver's seat? FEMS Immunol Med Microbiol 2006; 46:320.
  49. McCormick BA, Miller SI, Carnes D, Madara JL. Transepithelial signaling to neutrophils by salmonellae: a novel virulence mechanism for gastroenteritis. Infect Immun 1995; 63:2302.
  50. Jung HC, Eckmann L, Yang SK, et al. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J Clin Invest 1995; 95:55.
  51. Miao EA, Alpuche-Aranda CM, Dors M, et al. Cytoplasmic flagellin activates caspase-1 and secretion of interleukin 1beta via Ipaf. Nat Immunol 2006; 7:569.
  52. Sansonetti PJ, Phalipon A, Arondel J, et al. Caspase-1 activation of IL-1beta and IL-18 are essential for Shigella flexneri-induced inflammation. Immunity 2000; 12:581.
  53. Tsuji NM, Tsutsui H, Seki E, et al. Roles of caspase-1 in Listeria infection in mice. Int Immunol 2004; 16:335.
  54. Mariathasan S, Weiss DS, Dixit VM, Monack DM. Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis. J Exp Med 2005; 202:1043.
  55. Lara-Tejero M, Sutterwala FS, Ogura Y, et al. Role of the caspase-1 inflammasome in Salmonella typhimurium pathogenesis. J Exp Med 2006; 203:1407.
  56. Finlay BB, Falkow S. Virulence factors associated with Salmonella species. Microbiol Sci 1988; 5:324.
  57. Rahman MM, Guard-Petter J, Carlson RW. A virulent isolate of Salmonella enteritidis produces a Salmonella typhi-like lipopolysaccharide. J Bacteriol 1997; 179:2126.
  58. Kawasaki K, Ernst RK, Miller SI. 3-O-deacylation of lipid A by PagL, a PhoP/PhoQ-regulated deacylase of Salmonella typhimurium, modulates signaling through Toll-like receptor 4. J Biol Chem 2004; 279:20044.
  59. Khan SA, Everest P, Servos S, et al. A lethal role for lipid A in Salmonella infections. Mol Microbiol 1998; 29:571.
  60. Guo L, Lim KB, Gunn JS, et al. Regulation of lipid A modifications by Salmonella typhimurium virulence genes phoP-phoQ. Science 1997; 276:250.
  61. Bader MW, Sanowar S, Daley ME, et al. Recognition of antimicrobial peptides by a bacterial sensor kinase. Cell 2005; 122:461.
  62. Nishino K, Latifi T, Groisman EA. Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Mol Microbiol 2006; 59:126.
  63. Aguero J, Faundez G, Nunez M, et al. Choleriform syndrome and production of labile enterotoxin (CT/LT1)-like antigen by species of Salmonella infantis and Salmonella haardt isolated from the same patient. Rev Infect Dis 1991; 13:420.
  64. Chopra AK, Houston CW, Peterson JW, et al. Cloning and expression of the Salmonella enterotoxin gene. J Bacteriol 1987; 169:5095.
  65. Chopra AK, Huang JH, Xu X, et al. Role of Salmonella enterotoxin in overall virulence of the organism. Microb Pathog 1999; 27:155.
  66. Rahman H, Tschape H. Induction of Salmonella enterotoxin (stn) gene expression by epithelial cells (IEC-6). Indian J Exp Biol 1999; 37:1101.
  67. García-del Portillo F. Salmonella intracellular proliferation: where, when and how? Microbes Infect 2001; 3:1305.
  68. Alpuche-Aranda CM, Racoosin EL, Swanson JA, Miller SI. Salmonella stimulate macrophage macropinocytosis and persist within spacious phagosomes. J Exp Med 1994; 179:601.
  69. Miller SI, Kukral AM, Mekalanos JJ. A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. Proc Natl Acad Sci U S A 1989; 86:5054.
  70. Groisman EA, Chiao E, Lipps CJ, Heffron F. Salmonella typhimurium phoP virulence gene is a transcriptional regulator. Proc Natl Acad Sci U S A 1989; 86:7077.
  71. Angelakopoulos H, Hohmann EL. Pilot study of phoP/phoQ-deleted Salmonella enterica serovar typhimurium expressing Helicobacter pylori urease in adult volunteers. Infect Immun 2000; 68:2135.
  72. Fields PI, Swanson RV, Haidaris CG, Heffron F. Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A 1986; 83:5189.
  73. Guiney DG, Fang FC, Krause M, et al. Biology and clinical significance of virulence plasmids in Salmonella serovars. Clin Infect Dis 1995; 21 Suppl 2:S146.
  74. Libby SJ, Adams LG, Ficht TA, et al. The spv genes on the Salmonella dublin virulence plasmid are required for severe enteritis and systemic infection in the natural host. Infect Immun 1997; 65:1786.
  75. Ahmer BM, Tran M, Heffron F. The virulence plasmid of Salmonella typhimurium is self-transmissible. J Bacteriol 1999; 181:1364.
  76. Chiu CH, Chu C, Ou JT. Lack of evidence of an association between the carriage of virulence plasmid and the bacteremia of Salmonella typhimurium in humans. Microbiol Immunol 2000; 44:741.
  77. Chang CC, Ou JT. Excess production of interleukin-12 subunit p40 stimulated by the virulence plasmid of Salmonella enterica serovar Typhimurium in the early phase of infection in the mouse. Microb Pathog 2002; 32:15.
  78. Conlan JW. Neutrophils prevent extracellular colonization of the liver microvasculature by Salmonella typhimurium. Infect Immun 1996; 64:1043.
  79. Anand AJ, Glatt AE. Salmonella osteomyelitis and arthritis in sickle cell disease. Semin Arthritis Rheum 1994; 24:211.
  80. Mabey DC, Brown A, Greenwood BM. Plasmodium falciparum malaria and Salmonella infections in Gambian children. J Infect Dis 1987; 155:1319.
  81. Gopinath R, Keystone JS, Kain KC. Concurrent falciparum malaria and Salmonella bacteremia in travelers: report of two cases. Clin Infect Dis 1995; 20:706.
  82. Gendrel D, Kombila M, Beaudoin-Leblevec G, Richard-Lenoble D. Nontyphoidal salmonellal septicemia in Gabonese children infected with Schistosoma intercalatum. Clin Infect Dis 1994; 18:103.
  83. Wheat LJ, Rubin RH, Harris NL, et al. Systemic salmonellosis in patients with disseminated histoplasmosis. Case for 'macrophage blockade' caused by Histoplasma capsulatum. Arch Intern Med 1987; 147:561.
  84. Miao EA, Andersen-Nissen E, Warren SE, Aderem A. TLR5 and Ipaf: dual sensors of bacterial flagellin in the innate immune system. Semin Immunopathol 2007; 29:275.
  85. Ramos JM, García-Corbeira P, Aguado JM, et al. Clinical significance of primary vs. secondary bacteremia due to nontyphoid Salmonella in patients without AIDS. Clin Infect Dis 1994; 19:777.
  86. Gruenewald R, Blum S, Chan J. Relationship between human immunodeficiency virus infection and salmonellosis in 20- to 59-year-old residents of New York City. Clin Infect Dis 1994; 18:358.
  87. Levine WC, Buehler JW, Bean NH, Tauxe RV. Epidemiology of nontyphoidal Salmonella bacteremia during the human immunodeficiency virus epidemic. J Infect Dis 1991; 164:81.
  88. Thamlikitkul V, Dhiraputra C, Paisarnsinsup T, Chareandee C. Non-typhoidal Salmonella bacteraemia: clinical features and risk factors. Trop Med Int Health 1996; 1:443.
  89. Wolfe MS, Louria DB, Armstrong D, Blevins A. Salmonellosis in patients with neoplastic disease. A review of 100 episodes at Memorial Cancer Center over a 13-year period. Arch Intern Med 1971; 128:546.
  90. Tumbarello M, Tacconelli E, Caponera S, et al. The impact of bacteraemia on HIV infection. Nine years experience in a large Italian university hospital. J Infect 1995; 31:123.
  91. Mastroeni P, Simmons C, Fowler R, et al. Igh-6(-/-) (B-cell-deficient) mice fail to mount solid acquired resistance to oral challenge with virulent Salmonella enterica serovar typhimurium and show impaired Th1 T-cell responses to Salmonella antigens. Infect Immun 2000; 68:46.
  92. Forrest BD. Impairment of immunogenicity of Salmonella typhi Ty21a due to preexisting cross-reacting intestinal antibodies. J Infect Dis 1992; 166:210.
  93. MacLennan CA, Gilchrist JJ, Gordon MA, et al. Dysregulated humoral immunity to nontyphoidal Salmonella in HIV-infected African adults. Science 2010; 328:508.
  94. Endt K, Stecher B, Chaffron S, et al. The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea. PLoS Pathog 2010; 6:e1001097.
  95. Thiemann S, Smit N, Roy U, et al. Enhancement of IFNγ Production by Distinct Commensals Ameliorates Salmonella-Induced Disease. Cell Host Microbe 2017; 21:682.
  96. Eloe-Fadrosh EA, McArthur MA, Seekatz AM, et al. Impact of oral typhoid vaccination on the human gut microbiota and correlations with s. Typhi-specific immunological responses. PLoS One 2013; 8:e62026.
  97. Claudi B, Spröte P, Chirkova A, et al. Phenotypic variation of Salmonella in host tissues delays eradication by antimicrobial chemotherapy. Cell 2014; 158:722.
  98. Helaine S, Cheverton AM, Watson KG, et al. Internalization of Salmonella by macrophages induces formation of nonreplicating persisters. Science 2014; 343:204.