Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1995 Oct;63(10):3790–3795. doi: 10.1128/iai.63.10.3790-3795.1995

Contribution of urease to acid tolerance in Yersinia enterocolitica.

T F De Koning-Ward 1, R M Robins-Browne 1
PMCID: PMC173532  PMID: 7558281

Abstract

The stomach serves as a barrier to enteric infection because of the antibacterial effect of the hydrochloric acid in gastric juice. In this study, we tested the ability of the enteric pathogen Yersinia enterocolitica to tolerate a pH range of 2.0 to 6.0 and found that under the conditions of a normal human fasting stomach (pH < 3 and a gastric emptying time of 2 h), Y. enterocolitica is highly acid resistant, showing approximately 85% survival. The resistance of Y. enterocolitica to acid in vitro depended on the bacterial growth phase and the concentration of urea in the medium, being maximal during stationary phase in the presence of at least 0.3 mM urea. Urease-negative mutants of Y. enterocolitica were constructed by disrupting the urease gene complex of a virulent strain of serogroup O9. Compared with the wild type, these mutants showed an approximately 1,000-fold decrease in the ability to tolerate acid in vitro (< 0.08% survival) and a 10-fold reduction in viability after passage through the stomachs of mice. Complementation of the disrupted urease genes in trans restored the ability of urease-negative mutants to tolerate low pH in vitro and gastric acidity to approximately wild-type levels. These findings indicate that urease is responsible for acid resistance in Y. enterocolitica and suggest that urease contributes to the virulence of Y. enterocolitica by enhancing the likelihood of bacterial survival during passage through the stomach.

Full Text

The Full Text of this article is available as a PDF (244.3 KB).

Selected References

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

  1. Bottone E. J., Chester B., Malowany M. S., Allerhand J. Unusual Yersinia enterocolitica isolates not associated with mesenteric lymphadenitis. Appl Microbiol. 1974 May;27(5):858–861. doi: 10.1128/am.27.5.858-861.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Casadaban M. J., Cohen S. N. Analysis of gene control signals by DNA fusion and cloning in Escherichia coli. J Mol Biol. 1980 Apr;138(2):179–207. doi: 10.1016/0022-2836(80)90283-1. [DOI] [PubMed] [Google Scholar]
  3. Christensen W. B. Urea Decomposition as a Means of Differentiating Proteus and Paracolon Cultures from Each Other and from Salmonella and Shigella Types. J Bacteriol. 1946 Oct;52(4):461–466. doi: 10.1128/jb.52.4.461-466.1946. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cornelis G., Laroche Y., Balligand G., Sory M. P., Wauters G. Yersinia enterocolitica, a primary model for bacterial invasiveness. Rev Infect Dis. 1987 Jan-Feb;9(1):64–87. doi: 10.1093/clinids/9.1.64. [DOI] [PubMed] [Google Scholar]
  5. Cover T. L., Aber R. C. Yersinia enterocolitica. N Engl J Med. 1989 Jul 6;321(1):16–24. doi: 10.1056/NEJM198907063210104. [DOI] [PubMed] [Google Scholar]
  6. Ditta G., Schmidhauser T., Yakobson E., Lu P., Liang X. W., Finlay D. R., Guiney D., Helinski D. R. Plasmids related to the broad host range vector, pRK290, useful for gene cloning and for monitoring gene expression. Plasmid. 1985 Mar;13(2):149–153. doi: 10.1016/0147-619x(85)90068-x. [DOI] [PubMed] [Google Scholar]
  7. Drasar B. S., Shiner M., McLeod G. M. Studies on the intestinal flora. I. The bacterial flora of the gastrointestinal tract in healthy and achlorhydric persons. Gastroenterology. 1969 Jan;56(1):71–79. [PubMed] [Google Scholar]
  8. Dunn B. E., Campbell G. P., Perez-Perez G. I., Blaser M. J. Purification and characterization of urease from Helicobacter pylori. J Biol Chem. 1990 Jun 5;265(16):9464–9469. [PubMed] [Google Scholar]
  9. Foberg U., Frydén A., Kihlström E., Persson K., Weiland O. Yersinia enterocolitica septicemia: clinical and microbiological aspects. Scand J Infect Dis. 1986;18(4):269–279. doi: 10.3109/00365548609032337. [DOI] [PubMed] [Google Scholar]
  10. Foster J. W., Hall H. K. Adaptive acidification tolerance response of Salmonella typhimurium. J Bacteriol. 1990 Feb;172(2):771–778. doi: 10.1128/jb.172.2.771-778.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Giannella R. A., Broitman S. A., Zamcheck N. Influence of gastric acidity on bacterial and parasitic enteric infections. A perspective. Ann Intern Med. 1973 Feb;78(2):271–276. doi: 10.7326/0003-4819-78-2-271. [DOI] [PubMed] [Google Scholar]
  12. Glogau R., Hanna L., Jawetz E. Herpetic whitlow as part of genital virus infection. J Infect Dis. 1977 Nov;136(5):689–692. doi: 10.1093/infdis/136.5.689. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. HIGUCHI K., SMITH J. L. Studies on the nutrition and physiology of Pasteurella pestis. VI. A differential plating medium for the estimation of the mutation rate to avirulence. J Bacteriol. 1961 Apr;81:605–608. doi: 10.1128/jb.81.4.605-608.1961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hartland E. L., Green S. P., Phillips W. A., Robins-Browne R. M. Essential role of YopD in inhibition of the respiratory burst of macrophages by Yersinia enterocolitica. Infect Immun. 1994 Oct;62(10):4445–4453. doi: 10.1128/iai.62.10.4445-4453.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hirsch P. R., Beringer J. E. A physical map of pPH1JI and pJB4JI. Plasmid. 1984 Sep;12(2):139–141. doi: 10.1016/0147-619x(84)90059-3. [DOI] [PubMed] [Google Scholar]
  17. Iriarte M., Stainier I., Cornelis G. R. The rpoS gene from Yersinia enterocolitica and its influence on expression of virulence factors. Infect Immun. 1995 May;63(5):1840–1847. doi: 10.1128/iai.63.5.1840-1847.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. LIEBER C. S., LEFEVRE A. Ammonia as a source of gastric hypoacidity in patients with uremia. J Clin Invest. 1959 Aug;38(8):1271–1277. doi: 10.1172/JCI103902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lambert de Rouvroit C., Sluiters C., Cornelis G. R. Role of the transcriptional activator, VirF, and temperature in the expression of the pYV plasmid genes of Yersinia enterocolitica. Mol Microbiol. 1992 Feb;6(3):395–409. [PubMed] [Google Scholar]
  20. Manoil C., Beckwith J. TnphoA: a transposon probe for protein export signals. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8129–8133. doi: 10.1073/pnas.82.23.8129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Marshall B. J., Barrett L. J., Prakash C., McCallum R. W., Guerrant R. L. Urea protects Helicobacter (Campylobacter) pylori from the bactericidal effect of acid. Gastroenterology. 1990 Sep;99(3):697–702. doi: 10.1016/0016-5085(90)90957-3. [DOI] [PubMed] [Google Scholar]
  22. Miliotis M. D., Morris J. G., Jr, Cianciosi S., Wright A. C., Wood P. K., Robins-Browne R. M. Identification of a conjunctivitis-associated gene locus from the virulence plasmid of Yersinia enterocolitica. Infect Immun. 1990 Aug;58(8):2470–2477. doi: 10.1128/iai.58.8.2470-2477.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mobley H. L., Hausinger R. P. Microbial ureases: significance, regulation, and molecular characterization. Microbiol Rev. 1989 Mar;53(1):85–108. doi: 10.1128/mr.53.1.85-108.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mulder B., Michiels T., Simonet M., Sory M. P., Cornelis G. Identification of additional virulence determinants on the pYV plasmid of Yersinia enterocolitica W227. Infect Immun. 1989 Aug;57(8):2534–2541. doi: 10.1128/iai.57.8.2534-2541.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Prpic J. K., Robins-Browne R. M., Davey R. B. In vitro assessment of virulence in Yersinia enterocolitica and related species. J Clin Microbiol. 1985 Jul;22(1):105–110. doi: 10.1128/jcm.22.1.105-110.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tabrizi S. N., Robins-Browne R. M. Influence of a 70 kilobase virulence plasmid on the ability of Yersinia enterocolitica to survive phagocytosis in vitro. Microb Pathog. 1992 Sep;13(3):171–179. doi: 10.1016/0882-4010(92)90018-j. [DOI] [PubMed] [Google Scholar]
  27. Taylor R. K., Manoil C., Mekalanos J. J. Broad-host-range vectors for delivery of TnphoA: use in genetic analysis of secreted virulence determinants of Vibrio cholerae. J Bacteriol. 1989 Apr;171(4):1870–1878. doi: 10.1128/jb.171.4.1870-1878.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ubben D., Schmitt R. A transposable promoter and transposable promoter probes derived from Tn1721. Gene. 1987;53(1):127–134. doi: 10.1016/0378-1119(87)90100-4. [DOI] [PubMed] [Google Scholar]
  29. de Koning-Ward T. F., Ward A. C., Robins-Browne R. M. Characterisation of the urease-encoding gene complex of Yersinia enterocolitica. Gene. 1994 Jul 22;145(1):25–32. doi: 10.1016/0378-1119(94)90318-2. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES