Mechanisms of Salmonella enterica Serotype Typhimurium Intestinal Colonization

Caleb W. Dorsey; Manuela Raffatellu; Robert A. Kingsley; Andreas J. Bäumler

doi:10.1128/9781555817619.ch21

Chapter 21 : Mechanisms of Salmonella enterica Serotype Typhimurium Intestinal Colonization

Authors: Caleb W. Dorsey¹, Manuela Raffatellu¹, Robert A. Kingsley¹, Andreas J. Bäumler¹

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Affiliations: 1: Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University System Health Science Center, 407 Reynolds Medical Bldg, College Station, TX 77843-1114.

Content Type: Monograph

Publication Year: 2005

Category: Clinical Microbiology; Bacterial Pathogenesis

Book DOI: 10.1128/9781555817619

Chapter DOI: 10.1128/9781555817619.ch21

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Abstract:

The serotype associated most frequently with Salmonella, a diarrheal disease, is Salmonella enterica serotype Typhimurium. Serotype Typhimurium infection in calves is an excellent model for the intestinal pathology, host response, and disease syndrome observed in humans. The interaction of S. enterica serotype Typhimurium with the intestinal mucosa in calves and humans results in the recruitment of neutrophils whose presence is the histopathologic hallmark for the acute phase of Salmonella-induced enterocolitis. This neutrophilic infiltrate is associated with necrosis of the upper mucosa in large areas of the terminal ileum and colon. Serotype Typhimurium initiates interaction with epithelial cells by causing the formation of membrane ruffles, a process that results in bacterial internalization. This invasion process is mediated by a type III secretion system (T3SS-1) encoded by genes located on Salmonella pathogenicity island 1. The main function of the T3SS-1 is to translocate effector proteins into the cytosol of a host cell. Persistence of serotype Typhimurium in the mesenteric lymph nodes has also been described for apparently healthy cattle. The lipopolysaccharide (LPS) of serotype Enteritidis does not contain the O4 antigen but instead carries a tyvelose branch (O9 antigen) as the immunodominant epitope on the trisaccharide backbone of its O-antigen repeat unit.

Citation: Dorsey C, Raffatellu M, Kingsley R, Bäumler A. 2005. Mechanisms of Salmonella enterica Serotype Typhimurium Intestinal Colonization, p 301-312. In Nataro J, Cohen P, Mobley H, Weiser J (ed), Colonization of Mucosal Surfaces. ASM Press, Washington, DC. doi: 10.1128/9781555817619.ch21

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Mechanisms of Salmonella enterica Serotype Typhimurium Intestinal Colonization

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Figure 1

Comparison of the amino acid sequences deduced from fimbrial genes of S. enterica serotype Typhimurium strain LT-2 ( 69 ) with orthologues present in serotype Typhi strain CT-18 (Ty) ( 92 ), serotype Enteritidis phage type 4 (En) (http://www.sanger.ac.uk/Projects/Salmonella/ and http://www.salmonella.org/), E. coli K-12 strain MG1655 (K12) ( 11 ), and E. coli O157:H7 strain EDL933 (EHEC) ( 93 ). Serotype Typhimurium genes are indicated by arrows. Genes whose deduced amino acid sequences show homology to fimbrial chaperones and outer membrane fimbrial usher proteins are indicated as hatched and black arrows, respectively. The percent identity of deduced serotype Typhimurium amino acid sequences to orthologues (defined by the same location on the genome, as indicated by homology of flanking DNA regions) present in serotype Typhi, serotype Enteritidis, E. coli K-12, and E. coli O157:H7 are indicated below each arrow. Asterisks indicate that sequences were modified prior to the alignment to correct for truncations, frameshift mutations, or stop codons. NP, gene not present.

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Figure 1

References

/content/book/10.1128/9781555817619.chap21

1. Abreu, M. T.,, P. Vora,, E. Faure,, L. S. Thomas,, E. T. Arnold,, and M. Arditi. 2001. Decreased expression of Toll-like receptor- 4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide. J. Immunol. 167:1609–1616.

2. Ahmer, B. M.,, J. van Reeuwijk,, P. R. Watson,, T. S. Wallis,, and F. Heffron. 1999. Salmonella SirA is a global regulator of genes mediating enteropathogenesis. Mol. Microbiol. 31:971–982.

3. Anderson, R. M. 1995. Evolutionary pressures in the spread and persistence of infectious agents in vertebrate populations. Parasitology 111:S15–S31.

4. Bäckhed, F.,, and M. Hornef. 2003. Toll-like receptor 4-mediated signaling by epithelial surfaces: necessity or threat? Microbes Infect. 5:951–959.

5. Barrow, P. A.,, A. Berchieri, Jr.,, and O. al-Haddad. 1992. Serological response of chickens to infection with Salmonella gallinarum-S. pullorum detected by enzyme-linked immunosorbent assay. Avian Dis. 36:227–236.

6. Bäumler, A. J.,, A. J. Gilde,, R. M. Tsolis,, A. W. M. van der Velden,, B. M. M. Ahmer,, and F. Heffron. 1997. Contribution of horizontal gene transfer and deletion events to the development of distinctive patterns of fimbrial operons during evolution of Salmonella serotypes. J. Bacteriol. 179:317–322.

7. Bäumler, A. J.,, R. M. Tsolis,, F. Bowe,, J. G. Kusters,, S. Hoffmann,, and F. Heffron. 1996. The pef fimbrial operon of Salmonella typhimurium mediates adhesion to murine small intestine and is necessary for fluid accumulation in the infant mouse. Infect. Immun. 64:61–68.

8. Bäumler, A. J.,, R. M. Tsolis,, and F. Heffron. 1996. The lpf fimbrial operon mediates adhesion of Salmonella typhimurium to murine Peyer’s patches. Proc. Natl. Acad. Sci. USA 93:279–283.

9. Blanc-Potard, A. B.,, F. Solomon,, J. Kayser,, and E. A. Groisman. 1999. The SPI-3 pathogenicity island of salmonella enterica. J. Bacteriol. 181:998–1004.

10. Blaser, M. J.,, and L. S. Newman. 1982. A review of human salmonellosis. I. Infective dose. Rev. Infect. Dis. 4:1096–1106.

11. Blattner, F. R.,, G. Plunkett III,, C. A. Bloch,, N. T. Perna,, V. Burland,, M. Riley,, J. Colladovides,, J. D. Glasner,, C. K. Rode,, G. F. Mayhew,, J. Gregor,, N. W. Davis,, H. A. Kirkpatrick,, M. A. Goeden,, D. J. Rose,, B. Mau,, and Y. Shao. 1997. The complete genome sequence of Escherichia coli K-12. Science 277:1453–1474.

12. Buchwald, D. S.,, and M. J. Blaser. 1984. A review of human salmonellosis. II. Duration of excretion following infection with nontyphi Salmonella. Rev. Infect. Dis. 6:345–356.

13. Cario, E.,, and D. K. Podolsky. 2000. Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect. Immun. 68:7010–7017.

14. Cario, E.,, I. M. Rosenberg,, S. L. Brandwein,, P. L. Beck,, H. C. Reinecker,, and D. K. Podolsky. 2000. Lipopolysaccharide activates distinct signaling pathways in intestinal epithelial cell lines expressing Toll-like receptors. J. Immunol. 164:966–972.

15.Centers for Disease Control and Prevention. 1999. Salmonella Surveillance: Annual Tabulation Summary, 1998. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, Ga.

16. Chan, K.,, S. Baker,, C. C. Kim,, C. S. Detweiler,, G. Dougan,, and S. Falkow. 2003. Genomic comparison of Salmonella enterica serovars and Salmonella bongori by use of an S. enterica serovar Typhimurium DNA microarray. J. Bacteriol. 185: 553–563.

17. Clegg, S.,, B. K. Purcell,, and J. Pruckler. 1987. Characterization of genes encoding type 1 fimbriae of Klebsiella pneumoniae, Salmonella typhimurium, and Serratia marcescens. Infect. Immun. 55:281–287.

18. Collazo, C. M.,, and J. E. Galan. 1997. The invasion-associated type III system of Salmonella typhimurium directs the translocation of Sip proteins into the host cell. Mol. Microbiol. 24: 747–756.

19. Collinson, S. K.,, P. S. Doig,, J. L. Doran,, S. Clouthier,, T. J. Trust,, and W. W. Kay. 1993. Thin, aggregative fimbriae mediate binding of Salmonella enteritidis to fibronectin. J. Bacteriol. 175:12–18.

20. Day, D. W.,, B. K. Mandal,, and B. C. Morson. 1978. The rectal biopsy appearances in Salmonella colitis. Histopathology 2:117–131.

21. Duguid, J. P.,, E. S. Anderson,, and I. Campbell. 1966. Fimbriae and adhesive properties in salmonellae. J. Pathol. Bacteriol. 92:107–137.

22. Eckmann, L.,, J. R. Smith,, M. P. Housley,, M. B. Dwinell,, and M. F. Kagnoff. 2000. Analysis by high density cDNA arrays of altered gene expression in human intestinal epithelial cells in response to infection with the invasive enteric bacteria Salmonella. J. Biol. Chem. 275:14084–14094.

23. Edwards, P. R.,, and D. W. Bruner. 1943. The occurrence and distribution of Salmonella types in the United States. J. Infect. Dis. 72:58–67.

24. Emmerth, M.,, W. Goebel,, S. I. Miller,, and C. J. Hueck. 1999. Genomic subtraction identifies Salmonella typhimurium prophages, F-related plasmid sequences, and a novel fimbrial operon, stf, which are absent in Salmonella typhi. J. Bacteriol. 181:5652–5661.

25. Everest, P.,, J. Ketley,, S. Hardy,, G. Douce,, S. Khan,, J. Shea,, D. Holden,, D. Maskell,, and G. Dougan. 1999. Evaluation of Salmonella typhimurium mutants in a model of experimental gastroenteritis. Infect. Immun. 67:2815–2821.

26. Fallon, M. T.,, W. H. Benjamin, Jr.,, T. R. Schoeb,, and D. E. Briles. 1991. Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth. Infect. Immun. 59: 852–856.

27. Fallon, M. T.,, T. R. Schoeb,, W. H. Benjamin, Jr.,, J. R. Lindsey,, and D. E. Briles. 1989. Modulation of resistance to Salmonella typhimurium infection in mice by mouse hepatitis virus (MHV). Microb. Pathog. 6:81–91.

28. Folkesson, A.,, A. Advani,, S. Sukupolvi,, J. D. Pfeifer,, S. Normark,, and S. Lofdahl. 1999. Multiple insertions of fimbrial operons correlate with the evolution of Salmonella serovars responsible for human disease. Mol. Microbiol. 33:612–622.

29. Frances, C. L.,, T. A. Ryan,, B. D. Jones,, S. J. Smith,, and S. Falkow. 1993. Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria. Nature 364:639–642.

30. Friedrich, M. J.,, N. E. Kinsey,, J. Vila,, and R. J. Kadner. 1993. Nucleotide sequence of a 13.9 kb segment of the 90 kb virulence plasmid of Salmonella typhimurium: the presence of fimbrial biosynthetic genes. Mol. Microbiol. 8:543–558.

31. Frost, A. J.,, A. P. Bland,, and T. S. Wallis. 1997. The early dynamic response of the calf ileal epithelium to Salmonella typhimurium. Vet. Pathol. 34:369–386.

32. Fu, Y.,, and J. E. Galan. 1998. The Salmonella typhimurium tyrosine phosphatase SptP is translocated into host cells and disrupts the actin cytoskeleton. Mol. Microbiol. 27:359–368.

33. Fusunyan, R. D.,, N. N. Nanthakumar,, M. E. Baldeon,, and W. A. Walker. 2001. Evidence for an innate immune response in the immature human intestine: Toll-like receptors on fetal enterocytes. Pediatr. Res. 49:589–593.

34. Galán, J. E. 1999. Interaction of Salmonella with host cells through the centisome 63 type III secretion system. Curr. Opin. Microbiol. 2:46–50.

35. Galán, J. E.,, and R. Curtiss III. 1989. Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells. Proc. Natl. Acad. Sci. USA 86:6383–6387.

36. Galyov, E. E.,, M. W. Wood,, R. Rosqvist,, P. B. Mullan,, P. R. Watson,, S. Hedges,, and T. S. Wallis. 1997. A secreted effector protein of Salmonella dublin is translocated into eukaryotic cells and mediates inflammation and fluid secretion in infected ileal mucosa. Mol. Microbiol. 25:903–912.

37. Gewirtz, A. T.,, T. A. Navas,, S. Lyons,, P. J. Godowski,, and J. L. Madara. 2001. Cutting edge: bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression. J. Immunol. 167:1882–1885.

38. Gewirtz, A. T.,, A. M. Siber,, J. M. Madara,, and B. A. Mc- Cormick. 1999. Orchestration of neutrophil movement by intestinal epithelial cells in response to Salmonella typhimurium can be uncoupled from bacterial internalization. Infect. Immun. 67:608–617.

39. Gewirtz, A. T.,, P. O. Simon, Jr.,, C. K. Schmitt,, L. J. Taylor,, C. H. Hagedorn,, A. D. O’Brien,, A. S. Neish,, and J. L. Madara. 2001. Salmonella typhimurium translocates flagellin across intestinal epithelia, inducing a proinflammatory response. J. Clin. Investig. 107:99–109.

40. Girardin, S. E.,, I. G. Boneca,, L. A. Carneiro,, A. Antignac,, M. Jehanno,, J. Viala,, K. Tedin,, M. K. Taha,, A. Labigne,, U. Zahringer,, A. J. Coyle,, P. S. DiStefano,, J. Bertin,, P. J. Sansonetti,, and D. J. Philpott. 2003. Nod1 detects a unique muropeptide from gram-negative bacterial peptidoglycan. Science 300:1584–1587.

41. Grund, S.,, and R. Meyer. 1987. Fimbriae formation, disease form and vaccination in infection with Salmonella typhimurium variatio copenhagen (STMVC). Berl. Münch. Tierärztl. Wochenschr. 100:367–373. (In German.)

42. Grund, S.,, and A. Seiler. 1993. Electron microscopic studies of fimbriae and lectin phagocytosis of Salmonella typhimurium variety copenhagen (STMVC). Zentbl. Veterinaermed. Reihe B 40:105–112. (In German.)

43. Hardt, W. D.,, L. M. Chen,, K. E. Schuebel,, X. R. Bustelo,, and J. E. Galan. 1998. S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93:815–826.

44. Hardt, W. D.,, and J. E. Galan. 1997. A secreted Salmonella protein with homology to an avirulence determinant of plant pathogenic bacteria. Proc. Natl. Acad. Sci. USA 94:9887–9892.

45. Heithoff, D. M.,, E. Y. Enioutina,, R. A. Daynes,, R. L. Sinsheimer,, D. A. Low,, and M. J. Mahan. 2001. Salmonella DNA adenine methylase mutants confer cross-protective immunity. Infect. Immun. 69:6725–6730.

46. Hermiston, M. L.,, and J. I. Gordon. 1995. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science 270:1203–1207.

47. Hershberg, R. M. 2002. The epithelial cell cytoskeleton and intracellular trafficking. V. Polarized compartmentalization of antigen processing and Toll-like receptor signaling in intestinal epithelial cells. Am. J. Physiol. Ser. G 283:G833–G839.

48. Hormaeche, C. E.,, H. S. Joysey,, L. Desilva,, M. Izhar,, and B. A. Stocker. 1991. Immunity conferred by Aro- Salmonella live vaccines. Microb. Pathog. 10:149–158.

49. Hormaeche, C. E.,, P. Mastroeni,, J. A. Harrison,, R. Demarco de Hormaeche,, S. Svenson,, and B. A. Stocker. 1996. Protection against oral challenge three months after i.v. immunization of BALB/c mice with live Aro Salmonella typhimurium and Salmonella enteritidis vaccines is serotype (species)- dependent and only partially determined by the main LPS O antigen. Vaccine 14:251–259.

50. Hornef, M. W.,, T. Frisan,, A. Vandewalle,, S. Normark,, and A. Richter-Dahlfors. 2002. Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J. Exp. Med. 195:559–570.

51. Hornef, M. W.,, B. H. Normark,, A. Vandewalle,, and S. Normark. 2003. Intracellular recognition of lipopolysaccharide by toll-like receptor 4 in intestinal epithelial cells. J. Exp. Med. 198:1225–1235.

52. Humphries, A. D.,, M. Raffatellu,, S. Winter,, E. H. Weening,, R. A. Kingsley,, R. Droleskey,, S. Zhang,, J. Figueiredo,, S. Khare,, J. Nunes,, L. G. Adams,, R. M. Tsolis,, and A. J. Baumler. 2003. The use of flow cytometry to detect expression of subunits encoded by 11 Salmonella enterica serotype Typhimurium fimbrial operons. Mol. Microbiol. 48:1357–1376.

53. Hurd, H. S.,, J. K. Gailey,, J. D. McKean,, and M. H. Rostagno. 2001. Rapid infection in market-weight swine following exposure to a Salmonella typhimurium-contaminated environment. Am. J. Vet. Res. 62:1194–1197.

54. Inohara, N.,, Y. Ogura,, and G. Nunez. 2002. Nods: a family of cytosolic proteins that regulate the host response to pathogens. Curr. Opin. Microbiol. 5:76–80.

55. Jepson, M. A.,, B. Kenny,, and A. D. Leard. 2001. Role of sipA in the early stages of Salmonella typhimurium entry into epithelial cells. Cell. Microbiol. 3:417–426.

56. Jung, H. C.,, L. Eckmann,, S. K. Yang,, A. Panja,, J. Fierer,, E. Morzycka-Wroblewska,, and M. F. Kagnoff. 1995. A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. J. Clin. Investig. 95:55–65.

57. Kingsley, R. A.,, and A. J. Bäumler. 2000. Host adaptation and the emergence of infectious disease: the salmonella paradigm. Mol. Microbiol. 36:1006–1014.

58. Kingsley, R. A.,, A. D. Humphries,, E. H. Weening,, M. R. De Zoete,, S. Winter,, A. Papaconstantinopoulou,, G. Dougan,, and A. J. Bäumler. 2003. Molecular and phenotypic analysis of the CS54 island of Salmonella enterica serotype Typhimurium: identification of intestinal colonization and persistence determinants. Infect. Immun. 71:629–640.

59. Kingsley, R. A.,, A. M. Keestra,, M. R. de Zoete,, and A. J. Bäumler. 2004. The Shad adhesin binds to the cationic cradle of the fibronectin 13FnIII repeat module: evidence for molecular mimicry of heparin binding. Mol. Microbiol. 52:345–355.

60. Kingsley, R. A.,, R. L. Santos,, A. M. Keestra,, L. G. Adams,, and A. J. Bäumler. 2002. Salmonella enterica serotype Typhimurium ShdA is an outer membrane fibronectin-binding protein that is expressed in the intestine. Mol. Microbiol. 43:895–905.

61. Kingsley, R. A.,, K. van Amsterdam,, N. Kramer,, and A. J. Bäumler. 2000. The shdA gene is restricted to serotypes of Salmonella enterica subspecies I and contributes to efficient and prolonged fecal shedding. Infect. Immun. 68:2720–2727.

62. Kita, E.,, M. Emote,, D. Oku,, F. Nishikawa,, A. Hamburg,, N. Kamikaidou,, and S. Kashiba. 1992. Contribution of interferon gamma and membrane-associated interleukin 1 to the resistance to murine typhoid of Ityr mice. J. Leukoc. Biol. 51:244–250.

63. Krabisch, P.,, and P. Dorn. 1980. Epidemiologic significance of live vectors in the transmission of Salmonella infections in broiler flocks. Berl. Muench. Tieraerztl.Wochenschr. 93:232–235.

64. Kukkonen, M.,, T. Raunio,, R. Virkola,, K. Lahteenmaki,, P. H. Makela,, P. Klemm,, S. Clegg,, and T. K. Korhonen. 1993. Basement membrane carbohydrate as a target for bacterial adhesion: binding of type I fimbriae of Salmonella enterica and Escherichia coli to laminin. Mol. Microbiol. 7:229–237.

65. Licht, T. R.,, K. A. Krogfelt,, P. S. Cohen,, L. K. Poulsen,, J. Urbance,, and S. Molin. 1996. Role of lipopolysaccharide in colonization of the mouse intestine by Salmonella typhimurium studied by in situ hybridization. Infect. Immun. 64:3811–3817.

66. Lockman, H. A.,, and R. Curtiss III. 1992. Virulence of nontype 1-fimbriated and nonfimbriated nonflagellated Salmonella typhimurium mutants in murine typhoid fever. Infect. Immun. 60:491–496.

67. Madara, J. L.,, T. W. Patapoff,, B. Gillece-Castro,, S. P. Colgan,, C. A. Parkos,, C. Delp,, and R. J. Mrsny. 1993. 5′-Adenosine monophosphate is the neutrophil-derived paracrine factor that elicits chloride secretion from T84 intestinal epithelial cell monolayers. J. Clin. Investig. 91:2320–2325.

68. Matsumura, H.,, K. Onozuka,, Y. Terada,, Y. Nakano,, and M. Nakano. 1990. Effect of murine recombinant interferon-gamma in the protection of mice against Salmonella. Int. J. Immunopharmacol. 12:49–56.

69. McClelland, M.,, K. E. Sanderson,, J. Spieth,, S. W. Clifton,, P. Latreille,, L. Courtney,, S. Porwollik,, J. Ali,, M. Dante,, F. Du,, S. Hou,, D. Layman,, S. Leonard,, C. Nguyen,, K. Scott,, A. Holmes,, N. Grewal,, E. Mulvaney,, E. Ryan,, H. Sun,, L. Florea,, W. Miller,, T. Stoneking,, M. Nhan,, R. Waterston,, and R. K. Wilson. 2001. Complete genome sequence of Salmonella enterica serovar Typhimurium LT2. Nature 413:852–856.

70. McGovern, V. J.,, and L. J. Slavutin. 1979. Pathology of Salmonella colitis. Am. J. Surg. Pathol. 3:483–490.

71. McLaren, I. M.,, and C. Wray. 1991. Epidemiology of Salmonella typhimurium infection in calves: persistence of salmonellae on calf units. Vet. Rec. 129:461–462.

72. Mead, P. S.,, L. Slutsker,, V. Dietz,, L. F. McCaig,, J. S. Bresee,, C. Shapiro,, P. M. Griffin,, and R. V. Tauxe. 1999. Food-related illness and death in the United States. Emerg. Infect. Dis. 5:607–625.

73. Michetti, P.,, M. J. Mahan,, J. M. Slauch,, J. J. Mekalanos,, and M. R. Neutra. 1992. Monoclonal secretory immunoglobulin A protects mice against oral challenge with the invasive pathogen Salmonella typhimurium. Infect. Immun. 60:1786– 1792.

74. Michetti, P.,, N. Porta,, M. J. Mahan,, J. M. Slauch,, J. J. Mekalanos,, A. L. Blum,, J. P. Kraehenbuhl,, and M. R. Neutra. 1994. Monoclonal immunoglobulin A prevents adherence and invasion of polarized epithelial cell monolayers by Salmonella typhimurium. Gastroenterology 107:915–923.

75. Mills, D. M.,, V. Bajaj,, and C. A. Lee. 1995. A 40kb chromosomal fragment encoding Salmonella typhimurium invasion genes is absent from the corresponding region of the Escherichia coli K-12 chromosome. Mol. Microbiol. 15:749–759.

76. Mirold, S.,, K. Ehrbar,, A. Weissmuller,, R. Prager,, H. Tschape,, H. Russmann,, and W. D. Hardt. 2001. Salmonella host cell invasion emerged by acquisition of a mosaic of separate genetic elements, including Salmonella pathogenicity island 1 (SPI1), SPI5, and sopE2. J. Bacteriol. 183:2348–2358.

77. Monack, D. M.,, D. M. Bouley,, and S. Falkow. 2004. Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+/+ mice and can be reactivated by IFN-γ neutralization. J. Exp. Med. 199:231–241.

78. Moo, D.,, D. O’Boyle,, W. Mathers,, and A. J. Frost. 1980. The isolation of Salmonella from jejunal and caecal lymph nodes of slaughtered animals. Aust. Vet. J. 56:181–183.

79. Morrow, B. J.,, J. E. Graham,, and R. Curtiss III. 1999. Genomic subtractive hybridization and selective capture of transcribed sequences identify a novel Salmonella typhimurium fimbrial operon and putative transcriptional regulator that are absent from the Salmonella typhi genome. Infect. Immun. 67:5106–5116.

80. Naik, S.,, E. J. Kelly,, L. Meijer,, S. Pettersson,, and I. R. Sanderson. 2001. Absence of Toll-like receptor 4 explains endotoxin hyporesponsiveness in human intestinal epithelium. J. Pediatr. Gastroenterol. Nutr. 32:449–453.

81. Nanthakumar, N. N.,, R. D. Fusunyan,, I. Sanderson,, and W. A. Walker. 2000. Inflammation in the developing human intestine: a possible pathophysiologic contribution to necrotizing enterocolitis. Proc. Natl. Acad. Sci. USA 97:6043–6048.

82. Nau, G. J.,, J. F. Richmond,, A. Schlesinger,, E. G. Jennings,, E. S. Lander,, and R. A. Young. 2002. Human macrophage activation programs induced by bacterial pathogens. Proc. Natl. Acad. Sci. USA 99:1503–1508.

83. Nau, G. J.,, A. Schlesinger,, J. F. Richmond,, and R. A. Young. 2003. Cumulative Toll-like receptor activation in human macrophages treated with whole bacteria. J. Immunol. 170: 5203–5209.

84. Naughton, P. J.,, G. Grant,, S. Bardocz,, E. Allen-Vercoe,, M. J. Woodward,, and A. Pusztai. 2001. Expression of type 1 fimbriae (SEF 21) of Salmonella enterica serotype Enteritidis in the early colonisation of the rat intestine. J. Med. Microbiol. 50:191–197.

85. Neilsen, P. O.,, G. A. Zimmerman,, and T. M. McIntyre. 2001. Escherichia coli Braun lipoprotein induces a lipopolysaccharide- like endotoxic response from primary human endothelial cells. J. Immunol. 167:5231–5239.

86. Nevola, J. J.,, B. A. Stocker,, D. C. Laux,, and P. S. Cohen. 1985. Colonization of the mouse intestine by an avirulent Salmonella typhimurium strain and its lipopolysaccharide-defective mutants. Infect. Immun. 50:152–159.

87. Nicholson, B.,, and D. Low. 2000. DNA methylation-dependent regulation of pef expression in Salmonella typhimurium. Mol. Microbiol. 35:728–742.

88. Nicholson, T. L.,, and A. J. Bäumler. 2001. Salmonella enterica serotype Typhimurium elicits cross-immunity against a Salmonella enterica serotype Enteritidis strain expressing LP fimbriae from the lack promoter. Infect. Immun. 69:204–212.

89. Norris, T. L.,, and A. J. Bäumler. 1999. Phase variation of the lpf fimbrial operon is a mechanism to evade cross immunity between Salmonella serotypes. Proc. Natl. Acad. Sci. USA 96:13393–13398.

90. Norris, T. L.,, R. A. Kingsley,, and A. J. Bäumler. 1998. Expression and transcriptional control of the Salmonella typhimurium lpf fimbrial operon by phase variation. Mol. Microbiol. 29:311–320.

91. Onozuka, K.,, S. Shimada,, H. Yamasu,, Y. Osada,, and M. Nakano. 1993. Non-specific resistance induced by a low-toxic lipid A analogue, DT-5461, in murine salmonellosis. Int. J. Immunopharmacol. 15:657–664.

92. Parkhill, J.,, G. Dougan,, K. D. James,, N. R. Thomson,, D. Pickard,, J. Wain,, C. Churcher,, K. L. Mungall,, S. D. Bentley,, M. T. Holden,, M. Sebaihia,, S. Baker,, D. Basham,, K. Brooks,, T. Chillingworth,, P. Connerton,, A. Cronin,, P. Davis,, R. M. Davies,, L. Dowd,, N. White,, J. Farrar,, T. Feltwell,, N. Hamlin,, A. Haque,, T. T. Hien,, S. Holroyd,, K. Jagels,, A. Krogh,, T. S. Larsen,, S. Leather,, S. Moule,, P. O’Gaora,, C. Parry,, M. Quail,, K. Rutherford,, M. Simmonds,, J. Skelton,, K. Stevens,, S. Whitehead,, and B. G. Barrell. 2001. Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18. Nature 413: 848–852.

93. Perna, N. T.,, G. Plunkett III,, V. Burland,, B. Mau,, J. D. Glasner,, D. J. Rose,, G. F. Mayhew,, P. S. Evans,, J. Gregor,, H. A. Kirkpatrick,, G. Posfai,, J. Hackett,, S. Klink,, A. Boutin,, Y. Shao,, L. Miller,, E. J. Grotbeck,, N. W. Davis,, A. Lim,, E. T. Dimalanta,, K. D. Potamousis,, J. Apodaca,, T. S. Anantharaman,, J. Lin,, G. Yen,, D. C. Schwartz,, R. A. Welch,, and F. R. Blattner. 2001. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 409:529–533.

94. Porwollik, S.,, R. M. Wong,, and M. McClelland. 2002. Evolutionary genomics of Salmonella: gene acquisitions revealed by microarray analysis. Proc. Natl. Acad. Sci. USA 99:8956–8961.

95. Reeves, P. 1993. Evolution of Salmonella O antigen variation by interspecific gene transfer on a large scale. Trends Genet. 9:17–22.

96. Reis, B. P.,, S. Zhang,, R. M. Tsolis,, A. J. Bäumler,, L. G. Adams,, and R. L. Santos. 2003. The attenuated sopB mutant of Salmonella enterica serovar Typhimurium has the same tissue distribution and host chemokine response as the wild type in bovine Peyer’s patches. Vet. Microbiol. 97:269–277.

97. Romling, U.,, Z. Bian,, M. Hammar,, W. D. Sierralta,, and S. Normark. 1998. Curli fibers are highly conserved between Salmonella typhimurium and Escherichia coli with respect to operon structure and regulation. J. Bacteriol. 180:722–731.

98. Rosenberger, C. M.,, M. G. Scott,, M. R. Gold,, R. E. Hancock,, and B. B. Finlay. 2000. Salmonella typhimurium infection and lipopolysaccharide stimulation induce similar changes in macrophage gene expression. J. Immunol. 164:5894–5904.

99. Samuel, J. L.,, J. A. Eccles,, and J. Francis. 1981. Salmonella in the intestinal tract and associated lymph nodes of sheep and cattle. J. Hyg. 87:225–232.

100. Samuel, J. L.,, D. A. O’Boyle,, W. J. Mathers,, and A. J. Frost. 1979. Isolation of Salmonella from mesenteric lymph nodes of healthy cattle at slaughter. Res. Vet. Sci. 28:238–241.

101. Sansonetti, P. J.,, J. Arondel,, M. Huerre,, A. Harada,, and K. Matsushima. 1999. Interleukin-8 controls bacterial transepithelial translocation at the cost of epithelial destruction in experimental shigellosis. Infect. Immun. 67:1471–1480.

102. Santos, R. L.,, R. M. Tsolis,, S. Zhang,, T. A. Ficht,, A. J. Bäumler,, and L. G. Adams. 2001. Salmonella-induced cell death is not required for enteritis in calves. Infect. Immun. 69:4610–4617.

103. Santos, R. L.,, S. Zhang,, R. M. Tsolis,, A. J. Bäumler,, and L. G. Adams. 2002. Morphologic and molecular characterization of Salmonella typhimurium infection in neonatal calves. Vet. Pathol. 39:200–215.

104. Schmitt, C. K.,, J. S. Ikeda,, S. C. Darnell,, P. R. Watson,, J. Bispham,, T. S. Wallis,, D. L. Weinstein,, E. S. Metcalf,, and A. D. O’Brien. 2001. Absence of all components of the flagellar export and synthesis machinery differentially alters virulence of Salmonella enterica serovar Typhimurium in models of typhoid fever, survival in macrophages, tissue culture invasiveness, and calf enterocolitis. Infect. Immun. 69:5619–5625.

105. Sieling, P. A.,, and R. L. Modlin. 2002. Toll-like receptors: mammalian “taste receptors” for a smorgasbord of microbial invaders. Curr. Opin. Microbiol. 5:70–75.

106. Smith, B. P.,, G. W. Dilling,, J. K. House,, H. Konrad,, and N. Moore. 1995. Enzyme-linked immunosorbent assay for Salmonella serology using lipopolysaccharide antigen. J. Vet. Diagn. Investig. 7:481–487.

107. Smith, B. P.,, F. Habasha,, M. Reina-Guerra,, and A. J. Hardy. 1979. Bovine salmonellosis: experimental production and characterization of the disease in calves, using oral challenge with Salmonella typhimurium. Am. J. Vet. Res. 40:1510–1513.

108. Sojka, W. J.,, and H. I. Field. 1970. Salmonellosis in England and Wales 1958-1967. Vet. Bull. 40:515–531.

109. Stender, S.,, A. Friebel,, S. Linder,, M. Rohde,, S. Mirold,, and W. D. Hardt. 2000. Identification of SopE2 from Salmonella typhimurium, a conserved guanine nucleotide exchange factor for Cdc42 of the host cell. Mol. Microbiol. 36:1206–1221.

110. Sukupolvi, S.,, R. G. Lorenz,, J. I. Gordon,, Z. Bian,, J. D. Pfeifer,, S. J. Normark,, and M. Rhen. 1997. Expression of thin aggregative fimbriae promotes interaction of Salmonella typhimurium SR-11 with mouse small intestinal epithelial cells. Infect. Immun. 65:5320–5325.

111. Swenson, D. L.,, and S. Clegg. 1992. Identification of ancillary fim genes affecting fimA expression in Salmonella typhimurium. J. Bacteriol. 174:7697–7704.

112. Townsend, S. M.,, N. E. Kramer,, R. Edwards,, S. Baker,, N. Hamlin,, M. Simmonds,, K. Stevens,, S. Maloy,, J. Parkhill,, G. Dougan,, and A. J. Bäumler. 2001. Salmonella enterica serotype Typhi possesses a unique repertoire of fimbrial gene sequences. Infect. Immun. 69:2894–2901.

113. Tsolis, R. M.,, L. G. Adams,, T. A. Ficht,, and A. J. Bäumler. 1999. Contribution of Salmonella typhimurium virulence factors to diarrheal disease in calves. Infect. Immun. 67: 4879–4885.

114. Tsolis, R. M.,, L. G. Adams,, M. J. Hantman,, C. A. Scherer,, T. Kimborough,, R. A. Kingsley,, T. A. Ficht,, S. I. Miller,, and A. J. Bäumler. 2000. SspA is required for lethal Salmonella typhimurium infections in calves but is not essential for diarrhea. Infect. Immun. 68:3158–3163.

115. Tsolis, R. M.,, S. M. Townsend,, E. A. Miao,, S. I. Miller,, T. A. Ficht,, L. G. Adams,, and A. J. Bäumler. 1999. Identification of a putative Salmonella enterica serotype typhimurium host range factor with homology to IpaH and YopM by signature-tagged mutagenesis. Infect. Immun. 67:6385–6393.

116. Underhill, D. M.,, and A. Ozinsky. 2002. Toll-like receptors: key mediators of microbe detection. Curr. Opin. Immunol. 14:103–110.

117. van der Velden, A. W. M.,, A. J. Bäumler,, R. M. Tsolis,, and F. Heffron. 1998. Multiple fimbrial adhesins are required for full virulence of Salmonella typhimurium in mice. Infect. Immun. 66:2803–2808.

118. Wallis, T. S.,, M. Wood,, P. Watson,, S. Paulin,, M. Jones,, and E. Galyov. 1999. Sips, Sops, and SPIs but not stn influence Salmonella enteropathogenesis. Adv. Exp. Med. Biol. 473: 275–280.

119. Watson, P. R.,, E. E. Galyov,, S. M. Paulin,, P. W. Jones,, and T. S. Wallis. 1998. Mutation of invH, but not stn, reduces Salmonella-induced enteritis in cattle. Infect. Immun. 66: 1432–1438.

120. Wood, M. W.,, R. Rosqvist,, P. B. Mullan,, M. H. Edwards,, and E. E. Galyov. 1996. SopE, a secreted protein of Salmonella dublin, is translocated into the target eukaryotic cell via a sip-dependent mechanism and promotes bacterial entry. Mol. Microbiol. 22:327–338.

121. Wray, C.,, Y. E. Beedell,, and I. M. McLaren. 1991. A survey of antimicrobial resistance in salmonellae isolated from animals in England and Wales during 1984-1987. Br. Vet. J. 147:356–369.

122. Wray, C.,, and W. J. Sojka. 1978. Experimental Salmonella typhimurium infection in calves. Res. Vet. Sci. 25:139–143.

123. Wray, C.,, J. N. Todd,, and M. Hinton. 1987. Epidemiology of Salmonella typhimurium infection in calves: excretion of S. typhimurium in the faeces of calves in different management systems. Vet. Rec. 121:293–296.

124. Yang, S. K.,, L. Eckmann,, A. Panja,, and M. F. Kagnoff. 1997. Differential and regulated expression of C-X-C, C-C, and C-chemokines by human colon epithelial cells. Gastroenterology 113:1214–1223.

125. Zeng, H.,, A. Q. Carlson,, Y. Guo,, Y. Yu,, L. S. Collier-Hyams,, J. L. Madara,, A. T. Gewirtz,, and A. S. Neish. 2003. Flagellin is the major proinflammatory determinant of enteropathogenic Salmonella. J. Immunol. 171:3668–3674.

126. Zhang, S.,, L. G. Adams,, J. Nunes,, S. Khare,, R. M. Tsolis,, and A. J. Bäumler. 2003. Secreted effector proteins of Salmonella enterica serotype Typhimurium elicit host-specific chemokine profiles in animal models of typhoid fever and enterocolitis. Infect. Immun. 71:4795–4803.

127. Zhang, S.,, R. A. Kingsley,, R. L. Santos,, H. Andrews-Polymenis,, M. Raffatellu,, J. Figueiredo,, J. Nunes,, R. M. Tsolis,, L. G. Adams,, and A. J. Bäumler. 2003. Molecular pathogenesis of Salmonella enterica serotype Typhimurium-induced diarrhea. Infect. Immun. 71:1–12.

128. Zhang, S.,, R. L. Santos,, R. M. Tsolis,, S. Stender,, W.-D. Hardt,, A. J. Bäumler,, and L. G. Adams. 2002. SipA, SopA, SopB, SopD, and SopE2 act in concert to induce diarrhea in calves infected with Salmonella enterica serotype Typhimurium. Infect. Immun. 70:3843–3855.

129. Zhou, D.,, L. M. Chen,, L. Hernandez,, S. B. Shears,, and J. E. Galan. 2001. A Salmonella inositol polyphosphatase acts in conjunction with other bacterial effectors to promote host cell actin cytoskeleton rearrangements and bacterial internalization. Mol. Microbiol. 39:248–259.

130. Zhou, D.,, M. S. Mooseker,, and J. E. Galan. 1999. An invasion- associated Salmonella protein modulates the actinbundling activity of plastin. Proc. Natl. Acad. Sci. USA 96:10176–10181.

131. Zhou, D.,, M. S. Mooseker,, and J. E. Galan. 1999. Role of the S. typhimurium actin-binding protein SipA in bacterial internalization. Science 283:2092–2095.