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. 1991 Aug;59(8):2744–2749. doi: 10.1128/iai.59.8.2744-2749.1991

Mechanisms of fungal pathogenicity: correlation of virulence in vivo, susceptibility to killing by polymorphonuclear neutrophils in vitro, and neutrophil superoxide anion induction among Blastomyces dermatitidis isolates.

C J Morrison 1, D A Stevens 1
PMCID: PMC258081  PMID: 1649799

Abstract

Seven Blastomyces dermatitidis isolates varying in virulence for mice were compared for susceptibility to polymorphonuclear neutrophil (PMN) killing and the ability to induce superoxide anion (O2-) production by PMNs in vitro. In vitro killing of six B. dermatitidis isolates by murine peripheral blood PMNs or by PMNs elicited from the peritoneal cavity by a local immune reaction (B. dermatitidis-immune mice given killed B. dermatitidis intraperitoneally 24 h earlier) inversely correlated with in vivo virulence (most to least virulent) isolates: VV, V, V40, KL-1, A2, and GA-1). The capacity of isolates to induce O2- production by PMNs also inversely correlated with in vivo virulence. Isolate A, of intermediate in vivo virulence, was a good inducer of O2- production in vitro but was no more susceptible to in vitro killing by PMNs than isolate V, VV, or V40. Fungal intracellular superoxide dismutase or catalase content did not correlate with in vivo virulence or in vitro killing by PMNs. Isolate A, however, had two to four times the intracellular catalase activity as did other B. dermatitidis isolates, suggesting a possible mechanism for its enhanced resistance to in vitro killing by PMNs. Therefore, while in vitro killing by PMNs and the capacity to induce O2- production by PMNs inversely correlated with virulence for six B. dermatitidis isolates, isolate A was an exception: its resistance to killing by PMN-generated oxygen metabolites in vitro but its susceptibility to killing in vivo suggest that its in vivo killing occurs by other, perhaps nonoxidative, mechanisms.

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Selected References

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  1. BEERS R. F., Jr, SIZER I. W. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952 Mar;195(1):133–140. [PubMed] [Google Scholar]
  2. Babior B. M., Kipnes R. S., Curnutte J. T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744. doi: 10.1172/JCI107236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Badwey J. A., Karnovsky M. L. Active oxygen species and the functions of phagocytic leukocytes. Annu Rev Biochem. 1980;49:695–726. doi: 10.1146/annurev.bi.49.070180.003403. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Brummer E., Hanson L. H., Restrepo A., Stevens D. A. In vivo and in vitro activation of pulmonary macrophages by IFN-gamma for enhanced killing of Paracoccidioides brasiliensis or Blastomyces dermatitidis. J Immunol. 1988 Apr 15;140(8):2786–2789. [PubMed] [Google Scholar]
  7. Brummer E., Morozumi P. A., Philpott D. E., Stevens D. A. Virulence of fungi: correlation of virulence of Blastomyces dermatitidis in vivo with escape from macrophage inhibition of replication in vitro. Infect Immun. 1981 May;32(2):864–871. doi: 10.1128/iai.32.2.864-871.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brummer E., Morrison C. J., Stevens D. A. Recombinant and natural gamma-interferon activation of macrophages in vitro: different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi. Infect Immun. 1985 Sep;49(3):724–730. doi: 10.1128/iai.49.3.724-730.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brummer E., Stevens D. A. Activation of murine polymorphonuclear neutrophils for fungicidal activity with supernatants from antigen-stimulated immune spleen cell cultures. Infect Immun. 1984 Aug;45(2):447–452. doi: 10.1128/iai.45.2.447-452.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brummer E., Stevens D. A. Activation of pulmonary macrophages for fungicidal activity by gamma-interferon or lymphokines. Clin Exp Immunol. 1987 Dec;70(3):520–528. [PMC free article] [PubMed] [Google Scholar]
  11. Cox R. A., Best G. K. Cell wall composition of two strains of Blastomyces dermatitidis exhibiting differences in virulence for mice. Infect Immun. 1972 Apr;5(4):449–453. doi: 10.1128/iai.5.4.449-453.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cox R. A., Mills L. R., Best G. K., Denton J. F. Histologic reactions to cell walls of an avirulent and a virulent strain of Blastomyces dermatitidis. J Infect Dis. 1974 Feb;129(2):179–186. doi: 10.1093/infdis/129.2.179. [DOI] [PubMed] [Google Scholar]
  13. Crapo J. D., McCord J. M., Fridovich I. Preparation and assay of superoxide dismutases. Methods Enzymol. 1978;53:382–393. doi: 10.1016/s0076-6879(78)53044-9. [DOI] [PubMed] [Google Scholar]
  14. DENTON J. F., DISALVO A. F. ISOLATION OF BLASTOMYCES DERMATITIDIS FROM NATURAL SITES AT AUGUSTA, GEORGIA. Am J Trop Med Hyg. 1964 Sep;13:716–722. doi: 10.4269/ajtmh.1964.13.716. [DOI] [PubMed] [Google Scholar]
  15. DENTON J. F., McDONOUGH E. S., AJELLO L., AUSHERMAN R. J. Isolation of Blastomyces dermatitidis from soil. Science. 1961 Apr 14;133(3459):1126–1127. doi: 10.1126/science.133.3459.1126. [DOI] [PubMed] [Google Scholar]
  16. DISALVO A. F., DENTON J. F. LIPID CONTENT OF FOUR STRAINS OF BLASTOMYCES DERMATITIDIS OF DIFFERENT MOUSE VIRULENCE. J Bacteriol. 1963 Apr;85:927–931. doi: 10.1128/jb.85.4.927-931.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Drutz D. J., Frey C. L. Intracellular and extracellular defenses of human phagocytes against Blastomyces dermatitidis conidia and yeasts. J Lab Clin Med. 1985 Jun;105(6):737–750. [PubMed] [Google Scholar]
  18. Frey C. L., DeMarsh P. L., Drutz D. J. Divergent patterns of pulmonary blastomycosis induced by conidia and yeasts in athymic and euthymic mice. Am Rev Respir Dis. 1989 Jul;140(1):118–124. doi: 10.1164/ajrccm/140.1.118. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Hoeprich P. D., Finn P. D. Obfuscation of the activity of antifungal antimicrobics by culture media. J Infect Dis. 1972 Oct;126(4):353–361. doi: 10.1093/infdis/126.4.353. [DOI] [PubMed] [Google Scholar]
  21. Johnston R. B., Jr, Godzik C. A., Cohn Z. A. Increased superoxide anion production by immunologically activated and chemically elicited macrophages. J Exp Med. 1978 Jul 1;148(1):115–127. doi: 10.1084/jem.148.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Miyaji M., Nishimura K. Granuloma formation and killing functions of granuloma in congenitally athymic nude mice infected with Blastomyces dermatitidis and Paracoccidioides brasiliensis. Mycopathologia. 1983 Jun 20;82(3):129–141. doi: 10.1007/BF00439218. [DOI] [PubMed] [Google Scholar]
  24. Morozumi P. A., Brummer E., Stevens D. A. Protection against pulmonary blastomycosis: correlation with cellular and humoral immunity in mice after subcutaneous nonlethal infection. Infect Immun. 1982 Aug;37(2):670–678. doi: 10.1128/iai.37.2.670-678.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Morrison C. J., Brummer E., Isenberg R. A., Stevens D. A. Activation of murine polymorphonuclear neutrophils for fungicidal activity by recombinant gamma interferon. J Leukoc Biol. 1987 May;41(5):434–440. doi: 10.1002/jlb.41.5.434. [DOI] [PubMed] [Google Scholar]
  26. Morrison C. J., Brummer E., Stevens D. A. Effect of a local immune reaction on peripheral blood polymorphonuclear neutrophil microbicidal function: studies with fungal targets. Cell Immunol. 1987 Nov;110(1):176–182. doi: 10.1016/0008-8749(87)90111-0. [DOI] [PubMed] [Google Scholar]
  27. Morrison C. J., Brummer E., Stevens D. A. In vivo activation of peripheral blood polymorphonuclear neutrophils by gamma interferon results in enhanced fungal killing. Infect Immun. 1989 Oct;57(10):2953–2958. doi: 10.1128/iai.57.10.2953-2958.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Morrison C. J., Isenberg R. A., Stevens D. A. Enhanced oxidative mechanisms in immunologically activated versus elicited polymorphonuclear neutrophils: correlations with fungicidal activity. J Med Microbiol. 1988 Feb;25(2):115–121. doi: 10.1099/00222615-25-2-115. [DOI] [PubMed] [Google Scholar]
  29. Moser S. A., Koker P. J., Williams J. E. Fungal-strain-dependent alterations in the time course and mortality of chronic murine pulmonary blastomycosis. Infect Immun. 1988 Jan;56(1):34–39. doi: 10.1128/iai.56.1.34-39.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sasada M., Johnston R. B., Jr Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages. J Exp Med. 1980 Jul 1;152(1):85–98. doi: 10.1084/jem.152.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Schaffner A., Davis C. E., Schaffner T., Markert M., Douglas H., Braude A. I. In vitro susceptibility of fungi to killing by neutrophil granulocytes discriminates between primary pathogenicity and opportunism. J Clin Invest. 1986 Aug;78(2):511–524. doi: 10.1172/JCI112603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sixbey J. W., Fields B. T., Sun C. N., Clark R. A., Nolan C. M. Interactions between human granulocytes and Blastomyces dermatitidis. Infect Immun. 1979 Jan;23(1):41–44. doi: 10.1128/iai.23.1.41-44.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sugar A. M., Chahal R. S., Brummer E., Stevens D. A. Susceptibility of Blastomyces dermatitidis strains to products of oxidative metabolism. Infect Immun. 1983 Sep;41(3):908–912. doi: 10.1128/iai.41.3.908-912.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sugar A. M., Chahal R. S., Brummer E., Stevens D. A. The iron-hydrogen peroxide-iodide system is fungicidal: activity against the yeast phase of Blastomyces dermatitidis. J Leukoc Biol. 1984 Oct;36(4):545–548. doi: 10.1002/jlb.36.4.545. [DOI] [PubMed] [Google Scholar]
  35. Sugar A. M., Field K. G. Characteristics of the pulmonary cellular immune response to two strains of Blastomyces dermatitidis in the mouse. Am Rev Respir Dis. 1985 Dec;132(6):1319–1323. doi: 10.1164/arrd.1985.132.6.1319. [DOI] [PubMed] [Google Scholar]
  36. Sugar A. M., Picard M. Experimental blastomycosis pneumonia in mice by infection with conidia. J Med Vet Mycol. 1988;26(6):321–326. doi: 10.1080/02681218880000461. [DOI] [PubMed] [Google Scholar]

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