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. 1995 Sep;63(9):3642–3648. doi: 10.1128/iai.63.9.3642-3648.1995

Increased protein secretion and adherence to HeLa cells by Shigella spp. following growth in the presence of bile salts.

L M Pope 1, K E Reed 1, S M Payne 1
PMCID: PMC173505  PMID: 7642302

Abstract

Growth of Shigella spp. in the presence of the bile salt deoxycholate or chenodeoxycholate enhanced the bacterial invasion of HeLa cells. Growth in the presence of other structurally similar bile salts or detergents had little or no effect. Deoxycholate-enhanced invasion was not observed when bacteria were exposed to deoxycholate at low temperatures or when chloramphenicol was added to the growth medium, indicating that bacterial growth and protein synthesis are required. Increased invasion is associated with the presence of an intact Shigella virulence plasmid and is correlated with increased secretion of a set of proteins, including the Ipa proteins, to the outer membrane and into the growth medium. The increased invasion induced by the bile salts appears to be due to increased adherence. The enhanced adherence was specific to Shigella spp., since the enteroinvasive Escherichia coli strains tested did not exhibit the effect in response to growth in bile salts.

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Selected References

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  1. Allaoui A., Sansonetti P. J., Parsot C. MxiD, an outer membrane protein necessary for the secretion of the Shigella flexneri lpa invasins. Mol Microbiol. 1993 Jan;7(1):59–68. doi: 10.1111/j.1365-2958.1993.tb01097.x. [DOI] [PubMed] [Google Scholar]
  2. Allaoui A., Sansonetti P. J., Parsot C. MxiJ, a lipoprotein involved in secretion of Shigella Ipa invasins, is homologous to YscJ, a secretion factor of the Yersinia Yop proteins. J Bacteriol. 1992 Dec;174(23):7661–7669. doi: 10.1128/jb.174.23.7661-7669.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrews G. P., Hromockyj A. E., Coker C., Maurelli A. T. Two novel virulence loci, mxiA and mxiB, in Shigella flexneri 2a facilitate excretion of invasion plasmid antigens. Infect Immun. 1991 Jun;59(6):1997–2005. doi: 10.1128/iai.59.6.1997-2005.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bernardini M. L., Fontaine A., Sansonetti P. J. The two-component regulatory system ompR-envZ controls the virulence of Shigella flexneri. J Bacteriol. 1990 Nov;172(11):6274–6281. doi: 10.1128/jb.172.11.6274-6281.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dai J. H., Lee Y. S., Wong H. C. Effects of iron limitation on production of a siderophore, outer membrane proteins, and hemolysin and on hydrophobicity, cell adherence, and lethality for mice of Vibrio parahaemolyticus. Infect Immun. 1992 Jul;60(7):2952–2956. doi: 10.1128/iai.60.7.2952-2956.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DuPont H. L., Formal S. B., Hornick R. B., Snyder M. J., Libonati J. P., Sheahan D. G., LaBrec E. H., Kalas J. P. Pathogenesis of Escherichia coli diarrhea. N Engl J Med. 1971 Jul 1;285(1):1–9. doi: 10.1056/NEJM197107012850101. [DOI] [PubMed] [Google Scholar]
  7. Formal S. B., Hale T. L., Sansonetti P. J. Invasive enteric pathogens. Rev Infect Dis. 1983 Sep-Oct;5 (Suppl 4):S702–S707. doi: 10.1093/clinids/5.supplement_4.s702. [DOI] [PubMed] [Google Scholar]
  8. Gorden J., Small P. L. Acid resistance in enteric bacteria. Infect Immun. 1993 Jan;61(1):364–367. doi: 10.1128/iai.61.1.364-367.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gordon G. S., Moses A. C., Silver R. D., Flier J. S., Carey M. C. Nasal absorption of insulin: enhancement by hydrophobic bile salts. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7419–7423. doi: 10.1073/pnas.82.21.7419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hale T. L., Formal S. B. Protein synthesis in HeLa or Henle 407 cells infected with Shigella dysenteriae 1, Shigella flexneri 2a, or Salmonella typhimurium W118. Infect Immun. 1981 Apr;32(1):137–144. doi: 10.1128/iai.32.1.137-144.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hale T. L. Genetic basis of virulence in Shigella species. Microbiol Rev. 1991 Jun;55(2):206–224. doi: 10.1128/mr.55.2.206-224.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hale T. L., Oaks E. V., Formal S. B. Identification and antigenic characterization of virulence-associated, plasmid-coded proteins of Shigella spp. and enteroinvasive Escherichia coli. Infect Immun. 1985 Dec;50(3):620–629. doi: 10.1128/iai.50.3.620-629.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hale T. L., Sansonetti P. J., Schad P. A., Austin S., Formal S. B. Characterization of virulence plasmids and plasmid-associated outer membrane proteins in Shigella flexneri, Shigella sonnei, and Escherichia coli. Infect Immun. 1983 Apr;40(1):340–350. doi: 10.1128/iai.40.1.340-350.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Headley V. L., Payne S. M. Differential protein expression by Shigella flexneri in intracellular and extracellular environments. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4179–4183. doi: 10.1073/pnas.87.11.4179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. High N., Mounier J., Prévost M. C., Sansonetti P. J. IpaB of Shigella flexneri causes entry into epithelial cells and escape from the phagocytic vacuole. EMBO J. 1992 May;11(5):1991–1999. doi: 10.1002/j.1460-2075.1992.tb05253.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huang C. T., Woodward W. E., Hornick R. B., Rodriguez J. T., Nichols B. L. Fecal steroids in diarrhea. I. Acute shigellosis. Am J Clin Nutr. 1976 Sep;29(9):949–955. doi: 10.1093/ajcn/29.9.949. [DOI] [PubMed] [Google Scholar]
  17. Inouye M., Guthrie J. P. A mutation which changes a membrane protein of E. coli. Proc Natl Acad Sci U S A. 1969 Nov;64(3):957–961. doi: 10.1073/pnas.64.3.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Labrec E. H., Schneider H., Magnani T. J., Formal S. B. EPITHELIAL CELL PENETRATION AS AN ESSENTIAL STEP IN THE PATHOGENESIS OF BACILLARY DYSENTERY. J Bacteriol. 1964 Nov;88(5):1503–1518. doi: 10.1128/jb.88.5.1503-1518.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  20. Lawlor K. M., Payne S. M. Aerobactin genes in Shigella spp. J Bacteriol. 1984 Oct;160(1):266–272. doi: 10.1128/jb.160.1.266-272.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Maurelli A. T., Baudry B., d'Hauteville H., Hale T. L., Sansonetti P. J. Cloning of plasmid DNA sequences involved in invasion of HeLa cells by Shigella flexneri. Infect Immun. 1985 Jul;49(1):164–171. doi: 10.1128/iai.49.1.164-171.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Maurelli A. T., Blackmon B., Curtiss R., 3rd Temperature-dependent expression of virulence genes in Shigella species. Infect Immun. 1984 Jan;43(1):195–201. doi: 10.1128/iai.43.1.195-201.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mills J. A., Buysse J. M., Oaks E. V. Shigella flexneri invasion plasmid antigens B and C: epitope location and characterization with monoclonal antibodies. Infect Immun. 1988 Nov;56(11):2933–2941. doi: 10.1128/iai.56.11.2933-2941.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ménard R., Sansonetti P. J., Parsot C. Nonpolar mutagenesis of the ipa genes defines IpaB, IpaC, and IpaD as effectors of Shigella flexneri entry into epithelial cells. J Bacteriol. 1993 Sep;175(18):5899–5906. doi: 10.1128/jb.175.18.5899-5906.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ménard R., Sansonetti P., Parsot C. The secretion of the Shigella flexneri Ipa invasins is activated by epithelial cells and controlled by IpaB and IpaD. EMBO J. 1994 Nov 15;13(22):5293–5302. doi: 10.1002/j.1460-2075.1994.tb06863.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Oaks E. V., Hale T. L., Formal S. B. Serum immune response to Shigella protein antigens in rhesus monkeys and humans infected with Shigella spp. Infect Immun. 1986 Jul;53(1):57–63. doi: 10.1128/iai.53.1.57-63.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Parsot C., Ménard R., Gounon P., Sansonetti P. J. Enhanced secretion through the Shigella flexneri Mxi-Spa translocon leads to assembly of extracellular proteins into macromolecular structures. Mol Microbiol. 1995 Apr;16(2):291–300. doi: 10.1111/j.1365-2958.1995.tb02301.x. [DOI] [PubMed] [Google Scholar]
  28. Payne S. M., Finkelstein R. A. Detection and differentiation of iron-responsive avirulent mutants on Congo red agar. Infect Immun. 1977 Oct;18(1):94–98. doi: 10.1128/iai.18.1.94-98.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Roda A., Hofmann A. F., Mysels K. J. The influence of bile salt structure on self-association in aqueous solutions. J Biol Chem. 1983 May 25;258(10):6362–6370. [PubMed] [Google Scholar]
  30. Sansonetti P. J. Genetic and molecular basis of epithelial cell invasion by Shigella species. Rev Infect Dis. 1991 Mar-Apr;13 (Suppl 4):S285–S292. doi: 10.1093/clinids/13.supplement_4.s285. [DOI] [PubMed] [Google Scholar]
  31. Sasakawa C., Komatsu K., Tobe T., Suzuki T., Yoshikawa M. Eight genes in region 5 that form an operon are essential for invasion of epithelial cells by Shigella flexneri 2a. J Bacteriol. 1993 Apr;175(8):2334–2346. doi: 10.1128/jb.175.8.2334-2346.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Seltmann G., Pál T., Tschäpe H. Surface hydrophobicity of plasmid-carrying virulent Shigella flexneri and their avirulent variants. J Basic Microbiol. 1986;26(5):283–287. doi: 10.1002/jobm.3620260508. [DOI] [PubMed] [Google Scholar]
  33. Stugard C. E., Daskaleros P. A., Payne S. M. A 101-kilodalton heme-binding protein associated with congo red binding and virulence of Shigella flexneri and enteroinvasive Escherichia coli strains. Infect Immun. 1989 Nov;57(11):3534–3539. doi: 10.1128/iai.57.11.3534-3539.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Venkatesan M. M., Buysse J. M., Oaks E. V. Surface presentation of Shigella flexneri invasion plasmid antigens requires the products of the spa locus. J Bacteriol. 1992 Mar;174(6):1990–2001. doi: 10.1128/jb.174.6.1990-2001.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

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