Studies on Phase Transitions in the Dimorphic Pathogen Histoplasma capsulatum

  • G. S. Kobayashi
  • G. Medoff
  • B. Maresca
  • M. Sacco
  • B. V. Kumar


Histoplasma capsulatum, the etiological agent of histoplasmosis, is a dimorphic pathogenic fungus. The disease histoplasmosis occurs in many different parts of the world, but has a particularly high prevalence in temperate and subtropical zones such as the Ohio and Mississippi river valleys of the United States, South and Central America, parts of the Mediterranean basin, and West Africa (P. Q. Edwards and Billings, 1971). The epidemiology of H. capsulatum and problems related to human infection have been extensively studied (Sweany, 1960; Ajello et al., 1971; Schwarz, 1981). The nature of dimorphism in H. capsulatum has also received a great deal of interest ever since the fungus was observed in tissue and cultured in vitro and discovered to have a saprophytic hyphal phase and a parasitic yeast phase (DeMonbreun, 1934).


Yeast Cell Alternate Oxidase Shunt Pathway Hyphal Cell Histoplasma Capsulatum 
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  1. Ajello, L., Chick, E. W., and Furcolow, M. L., 1971, Histoplasmosis, Proceedings of the Second National Conference, Charles C Thomas, Springfield, Illinois.Google Scholar
  2. Ashburner, M., and Bonner, J., 1979, The induction of gene activity in Drosophila by heat shock, Cell 17:241–254.PubMedCrossRefGoogle Scholar
  3. Berliner, M. D., 1968, Primary subcultures of Histoplasma capsulatum: Macro-and micro-morphology of the mycelial phase, Sabouraudia 6:111–118.PubMedCrossRefGoogle Scholar
  4. Boguslawski, G., and Stetler, D. A., 1979, Aspects of physiology of Histoplasma capsulatum (a review), Mycopathologia 67:17–24.PubMedCrossRefGoogle Scholar
  5. Boguslawski, G., Schlessinger, D., Medoff, G., and Kobayashi, G. S., 1974, Ribonucleic acid polymerases of the yeast phase of Histoplasma capsulatum, J. Bacteriol. 118:481–485.Google Scholar
  6. Buguslawski, G., Akagi, J. M., and Ward, L. G., 1976, Possible role for cysteine biosynthesis in conversion from mycelial to yeast form of Histoplasma capsulatum, Nature (London) 261:336–338.CrossRefGoogle Scholar
  7. Byers, B., and Goetsch, L., 1974, Duplication of spindle plaques and integration of the yeast cell cycle, Cold Spring Harbor Symp. Quant. Biol. 38:123–131.PubMedCrossRefGoogle Scholar
  8. Byers, B., and Goetsch, L., 1975, Behavior of spindles and spindle plaques in the cell cycle and conjugation of Saccharomyces cerevisiae, J. Bacteriol. 124:511–523.PubMedGoogle Scholar
  9. Cheung, S. C., Kobayashi, G. S., Schlessinger, D., and Medoff, G., 1974, RNA metabolism during morphogenesis in Histoplasma capsulatum, J. Gen. Microbiol. 82:301–307.PubMedGoogle Scholar
  10. Cheung, S. C., Medoff, G., Schlessinger, D., and Kobayashi, G. S., 1975, Response of yeast and myeclial phases of Histoplasma capsulatum to amphotericin B and actinomycin D, Antimicrob. Agents Chemother. 8:498–503.PubMedGoogle Scholar
  11. Daniels, L. S., Berliner, M. D., and Campbell, C. C., 1968, Varying virulence in rabbits infected with different filamentous types of Histoplasma capsulatum, J. Bacteriol. 96:1535–1539.PubMedGoogle Scholar
  12. DeMonbreun, W. A., 1934, The cultivation and cultural characteristics of Darlings’ Histoplasma capsulatum, Am. J. Trop. Med. Hyg. 14:93–125.Google Scholar
  13. Edwards, M. R., Hazen, E. L., and Edwards, G. A., 1959, The fine structure of the yeast-like cells of Histoplasma capsulatum in culture, J. Gen. Microbiol. 20:496–593.PubMedGoogle Scholar
  14. Edwards, P. Q., and Billings, E. L., 1971, Worldwide pattern of skin sensitivity to histoplasmin, Am. J. Trop. Med. Hyg. 20:228–319.Google Scholar
  15. Fleck, A., and Munro, H. N., 1962, The precision of ultraviolet absorption measurements in the Schmidt-Thannhauser procedure for nucleic acid estimation, Biochim. Biophys. Acta 55:571–583.PubMedCrossRefGoogle Scholar
  16. Garrison, R. G., and Boyd, K. S., 1978, Electron microscopy of yeast-like cell development from the microconidium of Histoplasma capsulatum, J. Bacteriol. 133:345–353.PubMedGoogle Scholar
  17. Garrison, R. G., Dodd, H. T., and Hamilton, J. W., 1970, The uptake of low molecular weight sulfur-containing compounds by Histoplasma capsulatum and related dimorphic fungi, Mycopathologia 40:171–180.Google Scholar
  18. Gates, D. W., and Brownstein, B. H., 1980, Ribosomal RNA from the yeast and mycelial phases of Histoplasma capsulatum, Exp. Mycol. 4:231–238.CrossRefGoogle Scholar
  19. Gilardi, G. L., 1965, Nutrition of systemic and subcutaneous pathogenic fungi, Bacteriol. Rev. 29:406–424.PubMedGoogle Scholar
  20. Goodwin, R. A., Loyd, J. E., and DesPres, R. M., 1981, Histoplasmosis in normal hosts, Medicine 60:231–266.PubMedCrossRefGoogle Scholar
  21. Hoch, H. C., and Howard, R. J., 1980, Ultrastructure of freeze-substituted hyphae of the Basidiomycete Laetisaria arvalis, Protoplasma 103:281–297.CrossRefGoogle Scholar
  22. Howard, R. J., 1981, Ultrastructural analysis of hyphal tip cell growth in fungi: Spitzenkor-per, cytoskeleton and endomembranes after freeze-substitution, J. Cell Sci. 48:89–103.PubMedGoogle Scholar
  23. Howard, R. J., and Aist, J. R., 1979, Hyphal tip cell ultrastructure of the fungus Fusarium: Improved preservation by freeze-substitution, J. Ultrastruct. Res. 66:224–234.PubMedCrossRefGoogle Scholar
  24. Jacobson, E. S., and Harrell, A. C., 1981, Selenocystine-resistant mutants of Histoplasma capsulatum, Mycopathologia 73:177–181.PubMedCrossRefGoogle Scholar
  25. Jacobson, E. S., and Harrell, A. C., 1982, A prototrophic strain of Histoplasma capsulatum, Mycopathologia 77:65–68.PubMedCrossRefGoogle Scholar
  26. Kumar, B. V., McMillian, R. A., Medoff, G., Gutwein, M., and Kobayashi, G. S., 1980, Comparison of the ribonucleic acid polymerases from both phases of Histoplasma capsulatum, Biochemistry 19:1080–1087.PubMedCrossRefGoogle Scholar
  27. Kumar, B. V., Medoff, G., Painter, A., and Kobayashi, G. S., 1982, Antigenic differences between corresponding DNA-dependent RNA polymerases from both phases of Histoplasma capsulatum, Exp. Mycol. 6:90–94.CrossRefGoogle Scholar
  28. Kumar, B. V., Maresca, B., Sacco, M., Goewert, R., Kobayashi, G. S., and Medoff, G., 1983, Purification and characterization of a cysteine dioxygenase from the yeast phase of Histoplasma capsulatum, Biochemistry 22:762–768.PubMedCrossRefGoogle Scholar
  29. Kwon-Chung, K. J., 1972, Sexual stage of Histoplasma capsulatum, Science 175:326.PubMedCrossRefGoogle Scholar
  30. Kwon-Chung, K. J., 1973, Studies on Emmonsiella capsulata. I. Heterothallism and development of ascocarp, Mycologia 65:109–121.PubMedCrossRefGoogle Scholar
  31. Kwon-Chung, K. J., Weeks, R. J., and Larsh, H. W., 1974, Studies on Emmonsiella capsu-lata (Histoplasma capsulatum). II. Distribution of the 2 mating types in 13 endemic states of the U.S., Am. J. Epidemiol. 99:44–49.PubMedGoogle Scholar
  32. Lambowitz, A. M., and Slayman, C. W., 1971, Cyanide-resistant respiration in Neurospora crassa, J. Bacteriol. 108:1087–1096.PubMedGoogle Scholar
  33. Little, J. W., and Mount, D. W., 1982, The SOS regulatory system of Escherichia coli, Cell 29:11–22.PubMedCrossRefGoogle Scholar
  34. Maresca, B., Medoff, G., Schlessinger, D., Kobayashi, G. S., and Medoff, J., 1977, Regulation of dimorphism in the pathogenic fungus Histoplasma capsulatum, Nature (London) 266:447–448.CrossRefGoogle Scholar
  35. Maresca, B., Jacobson, E., Medoff, G., and Kobayashi, G. S., 1978, Cystine reductase in the dimorphic fungus Histoplasma capsulatum, J. Bacteriol. 135:987–992.PubMedGoogle Scholar
  36. Maresca, B., Lambowitz, A. M., Kobayashi, G. S., and Medoff, G., 1979, Respiration in the yeast and mycelial phases of Histoplasma capsulatum, J. Bacteriol. 138:647–649.PubMedGoogle Scholar
  37. Maresca, B., Lambowitz, A. M., Kumar, B. V., Grant, G., Kobayashi, G. S., and Medoff, G., 1981, Role of cysteine in regulating morphogenesis and mitochondrial activity in the dimorphic fungus Histoplasma capsulatum, Proc. Nat I. Acad. Sci. U.S.A. 78:4596–4600.CrossRefGoogle Scholar
  38. McVeigh, I., and Houston, W. E., 1972, Factors affecting mycelial to yeast phase conversion and growth of the yeast phase of Histoplasma capsulatum, Mycopathol. My col. 47:135–151.CrossRefGoogle Scholar
  39. Medoff, J., Jacobson, E., and Medoff, G., 1981, Regulation of dimorphism in Histoplasma capsulatum by cyclic adenosine 3′,5′-monophosphate, J. Bacteriol. 145:1452–1455.PubMedGoogle Scholar
  40. Morris, N. R., 1980, Chromosome structure and the molecular biology of mitosis in eukaryotic micro-organisms, in: The Eukaryotic Microbe (G. W. Gooday, D. Llloyd, and A. P. J. Trinci, eds.), Cambridge University Press, Cambridge, pp. 41–76.Google Scholar
  41. Pine, L., 1977, Histoplasma antigens: Their production, purification and uses, Contrib. Microbiol. Immunol. 3:138–168.Google Scholar
  42. Pine, L., and Peacock, C. L., 1958, Studies on the growth of Histoplasma capsulatum, J. Bacteriol. 75:167–174.PubMedGoogle Scholar
  43. Pine, L., and Webster, R. E., 1962, Conversion in strains of Histoplasma capsulatum, J. Bacteriol. 83:149–157.PubMedGoogle Scholar
  44. Reca, M. E., 1968, Reduction of a tetrazolium salt in determining growth activity of yeast-phase Histoplasma capsulatum, Appl. Microbiol. 16:236–238.PubMedGoogle Scholar
  45. Reca, M. E., and Campbell, C. C., 1967, Growth curves with yeast phase of Histoplasma capsulatum, Sabouraudia 5:267–273.CrossRefGoogle Scholar
  46. Rippon, J. W., 1968, Monitored environment system to control cell growth, morphology, and metabolic rate in fungi by oxidation-reduction potentials, Appl. Microbiol. 16:114–121.PubMedGoogle Scholar
  47. Sacco, M., Maresca, B., Kumar, B. V., Kobayashi, G. S., and Medoff, G., 1981, Temperature-and cyclic nucleotide-induced phase transitions of Histoplasma capsulatum, J. Bacteriol. 146:117–120.PubMedGoogle Scholar
  48. Salvin, S. B., 1947, Cultural studies on the yeast-like phase of Histoplasma capsulatum Darling, J. Bacteriol. 54:655–660.Google Scholar
  49. Salvin, S. B., 1949, Cysteine and related compounds in the growth of the yeast-like phase of Histoplasma capsulatum, J. Infect. Dis. 84:275–283.PubMedCrossRefGoogle Scholar
  50. Scherr, G. H., 1957, Studies on the dimorphism of Histoplasma capsulatum, Exp. Cell Res. 12:92–107.PubMedCrossRefGoogle Scholar
  51. Schwarz, J., 1981, Histoplasmosis, Praeger, New York.Google Scholar
  52. Stetler, D. A., and Boguslawski, G., 1979, Cysteine biosynthesis in the fungus, Histoplasma capsulatum, Sabouraudia 17:23–34.PubMedCrossRefGoogle Scholar
  53. Sweany, H. C., 1960, Histoplasmosis, Charles C Thomas, Springfield, Illinois.Google Scholar
  54. Szaniszlo, P. J., Jacobs, C. W., and Geis, P. A., 1983, Dimorphism: Morphological and biochemical aspects, in: Fungi Pathogenic for Humans and Animals, Part A, Biology (D. H. Howard, ed.), Marcel Dekker, New York, pp. 323–436.Google Scholar
  55. Tewari, R. P., and Berkhout, F. J., 1972, Comparative pathogenicity of albino and brown types of Histoplasma capsulatum for mice, J. Infect. Dis. 125:504–508.PubMedCrossRefGoogle Scholar
  56. Wheat, L. J., Slama, T. G., Norton, J. A., Kohler, R. B., Eitzen, H. E., French, M. L. V., and Sathapatayavongs, B., 1982, Risk factors for disseminated or fatal histoplasmosis: Analysis of a large urban outbreak, Ann. Intern. Med. 96:159–163.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • G. S. Kobayashi
    • 1
  • G. Medoff
    • 2
  • B. Maresca
    • 3
  • M. Sacco
    • 3
  • B. V. Kumar
    • 2
  1. 1.Divisions of Infectious Diseases, Dermatology, and Laboratory MedicineWashington University School of MedicineSt. LouisUSA
  2. 2.Division of Infectious DiseasesWashington University School of MedicineSt. LouisUSA
  3. 3.International Institute of Genetics and BiophysicsCNR10 NaplesItaly

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