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. 1989 Apr;57(4):1200–1210. doi: 10.1128/iai.57.4.1200-1210.1989

Differential clearance and host-pathogen interactions of YopE- and YopK- YopL- Yersinia pestis in BALB/c mice.

S C Straley 1, M L Cibull 1
PMCID: PMC313251  PMID: 2925246

Abstract

This study characterized infections in BALB/c mice by the nonpigmented Yersinia pestis KIM and its derivatives lacking the low-Ca2+-response virulence plasmid pCD1 or failing to express selected yersinial outer membrane proteins (YOPs). The parent Y. pestis showed net growth in the spleen by 2 h and in the liver after 7 h; exponential growth in both the liver and spleen culminated in death of the mice starting on day 4, with total bacterial numbers of less than 10(8) in the blood, liver, and spleen together. The histopathology progressed from microabscesses to extensive coagulative necrosis unaccompanied by further immigration of inflammatory cells. This, together with the relatively low bacterial numbers, suggests a toxigenic mechanism. YopE- or YopK- YopL- yersiniae were cleared from the spleen but grew in the liver after an initial lag. Their growth was curbed after 1 to 2 days and entered a plateau that lasted 5 to 6 days; viable numbers then decline rapidly. This suggests that these Yop- mutations distinguish, at least kinetically, between host responses in liver and spleen. Both strains caused acute inflammation in liver that evolved into structured lesions surrounded by progressively mononuclear inflammation suggestive of a granulomatous response. Accordingly, YOP E and YOPs K and L are necessary in the early days of the infection for net growth in spleen and prolonged growth in the liver; their absence is reflected morphologically by the emergence of cell-mediated immunity in the liver. The YopE- and YopK- YopL- mutants bound only slightly increased amounts of C3, suggesting that YOPs E, K, and L are protective through mechanisms other than interfering with the binding of complement.

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Selected References

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  1. BICHOWSKY-SLOMNICKI L., BEN-EFRAIM S. BIOLOGICAL ACTIVITIES IN EXTRACTS OF PASTEURELLA PESTIS AND THEIR RELATION TO THE "PH 6 ANTIGEN". J Bacteriol. 1963 Jul;86:101–111. doi: 10.1128/jb.86.1.101-111.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BURROWS T. W. Virulence of Pasteurella pestis. Nature. 1957 Jun 15;179(4572):1246–1247. doi: 10.1038/1791246a0. [DOI] [PubMed] [Google Scholar]
  3. Balligand G., Laroche Y., Cornelis G. Genetic analysis of virulence plasmid from a serogroup 9 Yersinia enterocolitica strain: role of outer membrane protein P1 in resistance to human serum and autoagglutination. Infect Immun. 1985 Jun;48(3):782–786. doi: 10.1128/iai.48.3.782-786.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brubaker R. R. The genus Yersinia: biochemistry and genetics of virulence. Curr Top Microbiol Immunol. 1972;57:111–158. doi: 10.1007/978-3-642-65297-4_4. [DOI] [PubMed] [Google Scholar]
  5. Bölin I., Portnoy D. A., Wolf-Watz H. Expression of the temperature-inducible outer membrane proteins of yersiniae. Infect Immun. 1985 Apr;48(1):234–240. doi: 10.1128/iai.48.1.234-240.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CAVANAUGH D. C., RANDALL R. The role of multiplication of Pasteurella pestis in mononuclear phagocytes in the pathogenesis of flea-borne plague. J Immunol. 1959 Oct;83:348–363. [PubMed] [Google Scholar]
  7. Castilho B. A., Olfson P., Casadaban M. J. Plasmid insertion mutagenesis and lac gene fusion with mini-mu bacteriophage transposons. J Bacteriol. 1984 May;158(2):488–495. doi: 10.1128/jb.158.2.488-495.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DULBECCO R., VOGT M. Plaque formation and isolation of pure lines with poliomyelitis viruses. J Exp Med. 1954 Feb;99(2):167–182. doi: 10.1084/jem.99.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ferber D. M., Brubaker R. R. Plasmids in Yersinia pestis. Infect Immun. 1981 Feb;31(2):839–841. doi: 10.1128/iai.31.2.839-841.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Forsberg A., Bölin I., Norlander L., Wolf-Watz H. Molecular cloning and expression of calcium-regulated, plasmid-coded proteins of Y. pseudotuberculosis. Microb Pathog. 1987 Feb;2(2):123–137. doi: 10.1016/0882-4010(87)90104-5. [DOI] [PubMed] [Google Scholar]
  11. Goguen J. D., Walker W. S., Hatch T. P., Yother J. Plasmid-determined cytotoxicity in Yersinia pestis and Yersinia pseudotuberculosis. Infect Immun. 1986 Mar;51(3):788–794. doi: 10.1128/iai.51.3.788-794.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goguen J. D., Yother J., Straley S. C. Genetic analysis of the low calcium response in Yersinia pestis mu d1(Ap lac) insertion mutants. J Bacteriol. 1984 Dec;160(3):842–848. doi: 10.1128/jb.160.3.842-848.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Heesemann J., Algermissen B., Laufs R. Genetically manipulated virulence of Yersinia enterocolitica. Infect Immun. 1984 Oct;46(1):105–110. doi: 10.1128/iai.46.1.105-110.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lian C. J., Hwang W. S., Pai C. H. Plasmid-mediated resistance to phagocytosis in Yersinia enterocolitica. Infect Immun. 1987 May;55(5):1176–1183. doi: 10.1128/iai.55.5.1176-1183.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lian C. J., Pai C. H. Inhibition of human neutrophil chemiluminescence by plasmid-mediated outer membrane proteins of Yersinia enterocolitica. Infect Immun. 1985 Jul;49(1):145–151. doi: 10.1128/iai.49.1.145-151.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Maskell D. J., Hormaeche C. E., Harrington K. A., Joysey H. S., Liew F. Y. The initial suppression of bacterial growth in a salmonella infection is mediated by a localized rather than a systemic response. Microb Pathog. 1987 Apr;2(4):295–305. doi: 10.1016/0882-4010(87)90127-6. [DOI] [PubMed] [Google Scholar]
  18. Montie T. C. Properties and pharmacological action of plague murine toxin. Pharmacol Ther. 1981;12(3):491–499. doi: 10.1016/0163-7258(81)90094-2. [DOI] [PubMed] [Google Scholar]
  19. O'Brien A. D., Metcalf E. S., Rosenstreich D. L. Defect in macrophage effector function confers Salmonella typhimurium susceptibility on C3H/HeJ mice. Cell Immunol. 1982 Mar 1;67(2):325–333. doi: 10.1016/0008-8749(82)90224-6. [DOI] [PubMed] [Google Scholar]
  20. Perry R. D., Brubaker R. R. Vwa+ phenotype of Yersinia enterocolitica. Infect Immun. 1983 Apr;40(1):166–171. doi: 10.1128/iai.40.1.166-171.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Perry R. D., Haddix P., Atkins E. B., Soughers T. K., Straley S. C. Regulation of expression of V antigen and outer membrane proteins in Yersinia pestis. Contrib Microbiol Immunol. 1987;9:173–178. [PubMed] [Google Scholar]
  22. Pollack C., Straley S. C., Klempner M. S. Probing the phagolysosomal environment of human macrophages with a Ca2+-responsive operon fusion in Yersinia pestis. 1986 Aug 28-Sep 3Nature. 322(6082):834–836. doi: 10.1038/322834a0. [DOI] [PubMed] [Google Scholar]
  23. Portnoy D. A., Wolf-Watz H., Bolin I., Beeder A. B., Falkow S. Characterization of common virulence plasmids in Yersinia species and their role in the expression of outer membrane proteins. Infect Immun. 1984 Jan;43(1):108–114. doi: 10.1128/iai.43.1.108-114.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sample A. K., Brubaker R. R. Post-translational regulation of Lcr plasmid-mediated peptides in pesticinogenic Yersinia pestis. Microb Pathog. 1987 Oct;3(4):239–248. doi: 10.1016/0882-4010(87)90057-x. [DOI] [PubMed] [Google Scholar]
  25. Sample A. K., Fowler J. M., Brubaker R. R. Modulation of the low-calcium response in Yersinia pestis via plasmid-plasmid interaction. Microb Pathog. 1987 Jun;2(6):443–453. doi: 10.1016/0882-4010(87)90051-9. [DOI] [PubMed] [Google Scholar]
  26. Sodeinde O. A., Sample A. K., Brubaker R. R., Goguen J. D. Plasminogen activator/coagulase gene of Yersinia pestis is responsible for degradation of plasmid-encoded outer membrane proteins. Infect Immun. 1988 Oct;56(10):2749–2752. doi: 10.1128/iai.56.10.2749-2752.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Straley S. C., Bowmer W. S. Virulence genes regulated at the transcriptional level by Ca2+ in Yersinia pestis include structural genes for outer membrane proteins. Infect Immun. 1986 Feb;51(2):445–454. doi: 10.1128/iai.51.2.445-454.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Straley S. C., Brubaker R. R. Localization in Yersinia pestis of peptides associated with virulence. Infect Immun. 1982 Apr;36(1):129–135. doi: 10.1128/iai.36.1.129-135.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Straley S. C., Harmon P. A. Growth in mouse peritoneal macrophages of Yersinia pestis lacking established virulence determinants. Infect Immun. 1984 Sep;45(3):649–654. doi: 10.1128/iai.45.3.649-654.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Straley S. C., Harmon P. A. Yersinia pestis grows within phagolysosomes in mouse peritoneal macrophages. Infect Immun. 1984 Sep;45(3):655–659. doi: 10.1128/iai.45.3.655-659.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Straley S. C. The plasmid-encoded outer-membrane proteins of Yersinia pestis. Rev Infect Dis. 1988 Jul-Aug;10 (Suppl 2):S323–S326. doi: 10.1093/cid/10.supplement_2.s323. [DOI] [PubMed] [Google Scholar]
  32. Tertti R., Eerola E., Lehtonen O. P., Ståhlberg T. H., Viander M., Toivanen A. Virulence-plasmid is associated with the inhibition of opsonization in Yersinia enterocolitica and Yersinia pseudotuberculosis. Clin Exp Immunol. 1987 May;68(2):266–274. [PMC free article] [PubMed] [Google Scholar]
  33. Une T., Brubaker R. R. In vivo comparison of avirulent Vwa- and Pgm- or Pstr phenotypes of yersiniae. Infect Immun. 1984 Mar;43(3):895–900. doi: 10.1128/iai.43.3.895-900.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Une T., Brubaker R. R. Roles of V antigen in promoting virulence and immunity in yersiniae. J Immunol. 1984 Oct;133(4):2226–2230. [PubMed] [Google Scholar]
  35. Une T., Nakajima R., Brubaker R. R. Roles of V antigen in promoting virulence in Yersiniae. Contrib Microbiol Immunol. 1987;9:179–185. [PubMed] [Google Scholar]
  36. Walker R. V. Plague toxins. A critical review. Curr Top Microbiol Immunol. 1967;41:23–42. doi: 10.1007/978-3-642-46062-3_2. [DOI] [PubMed] [Google Scholar]
  37. Williams J. E., Cavanaugh D. C. Chronic infections in laboratory rodents from inoculation of nonencapsulated plague bacilli (Yersinia pestis). Experientia. 1983 Apr 15;39(4):408–409. doi: 10.1007/BF01963151. [DOI] [PubMed] [Google Scholar]

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