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. 1988 Jan;56(1):34–39. doi: 10.1128/iai.56.1.34-39.1988

Fungal-strain-dependent alterations in the time course and mortality of chronic murine pulmonary blastomycosis.

S A Moser 1, P J Koker 1, J E Williams 1
PMCID: PMC259229  PMID: 3335407

Abstract

Intratracheal injection of 10(4) conidia of Blastomyces dermatitidis strain M1-A into mice was shown in previous work to induce chronic pulmonary and disseminated infection with histopathologic features of chronic human blastomycosis. Furthermore, 10-fold variations in inoculum density produced marked changes in mean survival times (MSTs), i.e., 32 days at 10(6), 36 days at 10(5), 97 days at 10(4), and 172 days at 10(3). A second strain (M1-B) failed to induce death in this model. To assess fungal-strain-dependent virulence, we extended these previous studies to 11 additional human isolates. Groups of male BALB/cByJ mice (6 to 8 weeks old) were injected intratracheally with 10(4) conidia from each of the 13 strains; the mice were weighed weekly and monitored for mortality, and their lungs were examined histopathologically. Infection rate and mortality were 100% in all groups except for the M1-B inoculated mice. For strains M1-B and M1-A, MST and mortality curves were not significantly different from those observed in our previously reported experiments. Four different survival patterns were noted in infected mice. The shortest MSTs were produced by strains M2-E, M2-B, M2-K, M2-H, and M2-A (24, 26, 26, 27, and 31 days, respectively), and the longest MST was seen in animal groups inoculated with strains M2-J and M2-G (130 and 134 days, respectively). Strains M2-I, M2-F, and M2-D produced intermediate MSTs of 65, 79, and 80 days, respectively. The 107-day MST induced by M1-A did not differ from strain M2-C-induced MST but differed significantly from the MST produced by the other strains. Pulmonary histopathology was similar in all animals dying with blastomycosis. The wide spectrum in survival times was not related to differences in clinical status of the patient from whom the isolate had been obtained, to fungal inoculum viability, or to individual mouse weight at inoculation. Strain-dependent virulence factors present in these fungal isolates alter the disease course in inbred mice in a fashion similar to that induced by 10-fold inoculum variation of strain M1-A conidia. These 13 isolates of B. dermatitidis, 1 avirulent and 12 with differing levels of virulence, provide tools for future studies into the nature of fungal virulence determinants in chronic blastomycosis.

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Selected References

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

  1. Baker R. D. Experimental Blastomycosis in Mice. Am J Pathol. 1942 May;18(3):463–477. [PMC free article] [PubMed] [Google Scholar]
  2. Brass C., Stevens D. A. Maturity as a critical determinant of resistance to fungal infections: studies in murine blastomycosis. Infect Immun. 1982 Apr;36(1):387–395. doi: 10.1128/iai.36.1.387-395.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brass C., Volkmann C. M., Klein H. P., Halde C. J., Archibald R. W., Stevens D. A. Pathogen factors and host factors in murine pulmonary blastomycosis. Mycopathologia. 1982 Jun 18;78(3):129–140. doi: 10.1007/BF00466066. [DOI] [PubMed] [Google Scholar]
  4. Brass C., Volkmann C. M., Philpott D. E., Klein H. P., Halde C. J., Stevens D. A. Spontaneous mutant of Blastomyces dermatitidis attenuated in virulence for mice. Sabouraudia. 1982 Jun;20(2):145–158. [PubMed] [Google Scholar]
  5. Deepe G. S., Jr, Taylor C. L., Bullock W. E. Evolution of inflammatory response and cellular immune responses in a murine model of disseminated blastomycosis. Infect Immun. 1985 Oct;50(1):183–189. doi: 10.1128/iai.50.1.183-189.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Denton J. F., Di Salvo A. F. Respiratory infection of laboratory animals with conidia of Blastomyces dermatitidis. Mycopathol Mycol Appl. 1968 Nov 13;36(2):129–136. doi: 10.1007/BF02049678. [DOI] [PubMed] [Google Scholar]
  7. Harvey R. P., Schmid E. S., Carrington C. C., Stevens D. A. Mouse model of pulmonary blastomycosis: utility, simplicity, and quantitative parameters. Am Rev Respir Dis. 1978 Apr;117(4):695–703. doi: 10.1164/arrd.1978.117.4.695. [DOI] [PubMed] [Google Scholar]
  8. Kaufman L., McLaughlin D. W., Clark M. J., Blumer S. Specific immunodiffusion test for blastomycosis. Appl Microbiol. 1973 Sep;26(3):244–247. doi: 10.1128/am.26.3.244-247.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Klein B. S., Kuritsky J. N., Chappell W. A., Kaufman L., Green J., Davies S. F., Williams J. E., Sarosi G. A. Comparison of the enzyme immunoassay, immunodiffusion, and complement fixation tests in detecting antibody in human serum to the A antigen of Blastomyces dermatitidis. Am Rev Respir Dis. 1986 Jan;133(1):144–148. doi: 10.1164/arrd.1986.133.1.144. [DOI] [PubMed] [Google Scholar]
  10. Landay M. E., Hotchi M., Soares N. Effect of prior vaccination on experimental blastomycosis. Mycopathol Mycol Appl. 1972 Jan 26;46(1):61–64. doi: 10.1007/BF02051896. [DOI] [PubMed] [Google Scholar]
  11. Morozumi P. A., Brummer E., Stevens D. A. Strain differences in resistance to infection reversed by route of challenge: studies in blastomycosis. Infect Immun. 1981 Nov;34(2):623–625. doi: 10.1128/iai.34.2.623-625.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Morozumi P. A., Halpern J. W., Stevens D. A. Susceptibility differences of inbred strains of mice to blastomycosis. Infect Immun. 1981 Apr;32(1):160–168. doi: 10.1128/iai.32.1.160-168.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. PINE L., DROUHET E. SUR L'OBTENTION ET LA CONSERVATION DE LA PHASE LEVURE D'HISTOPLASMA CAPSULATUM ET D'H. DUBOISI EN MILIEU CHIMIQUEMENT D'EFINI. Ann Inst Pasteur (Paris) 1963 Oct;105:798–804. [PubMed] [Google Scholar]
  14. Schwarz J., Salfelder K. Blastomycosis. A review of 152 cases. Curr Top Pathol. 1977;65:165–200. [PubMed] [Google Scholar]
  15. Vanek J., Schwarz J., Hakim S. North American blastomycosis: a study of ten cases. Am J Clin Pathol. 1970 Sep;54(3):384–400. doi: 10.1093/ajcp/54.3.384. [DOI] [PubMed] [Google Scholar]
  16. Williams J. E., Moser S. A. Chronic murine pulmonary blastomycosis induced by intratracheally inoculated Blastomyces dermatitidis conidia. Am Rev Respir Dis. 1987 Jan;135(1):17–25. doi: 10.1164/arrd.1987.135.1.17. [DOI] [PubMed] [Google Scholar]
  17. Williams J. E., Murphy R., Standard P. G., Phair J. P. Serologic response in blastomycosis: diagnostic value of double immunodiffusion assay. Am Rev Respir Dis. 1981 Feb;123(2):209–212. doi: 10.1164/arrd.1981.123.2.209. [DOI] [PubMed] [Google Scholar]

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