Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Aug;64(8):2930–2935. doi: 10.1128/iai.64.8.2930-2935.1996

Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media.

S Yan 1, E Nègre 1, J A Cashel 1, N Guo 1, C A Lyman 1, T J Walsh 1, D D Roberts 1
PMCID: PMC174169  PMID: 8757815

Abstract

Fibronectin (FN) is a major component of host extracellular matrix that may play an important role in the initiation and dissemination of Candida albicans infections. Expression of FN binding requires growth of C albicans blastoconidia in complex medium, and the regulation of FN receptor expression is poorly understood. We now demonstrate that hemoglobin is a potent and specific inducer of FN receptor expression and describe a defined medium supplemented with hemoglobin that greatly and stably enhances the binding activity of C. albicans for soluble FN. Enhancement of FN binding by hemoglobin in strain 44807 was concentration dependent and was maximal at 0.1% hemoglobin with 20- to 80-fold enhancement. The hemoglobin-induced FN binding to C. albicans was saturable, with a Kd of 2.7 X 10(-8) M. Enhancement required growth of C. albicans in hemoglobin-containing medium, since simply exposing blastoconidia to hemoglobin in a nongrowing status did not enhance binding. Induction was reversible following removal of hemoglobin from the growth medium and not associated with germination. Inorganic or protein-bound iron was not sufficient for the induction, since other iron-containing proteins or inorganic iron salts were inactive. Growth in the simple medium yeast nitrogen base supplemented with hemoglobin increased cell adhesion to immobilized FN and to cultured monolayers of bovine corneal endothelial cells. These data suggest that hemoglobin may be an important regulator of FN binding activity in C. albicans and thus may play a role in its pathogenesis.

Full Text

The Full Text of this article is available as a PDF (223.2 KB).

Selected References

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

  1. Bailey A., Wadsworth E., Calderone R. Adherence of Candida albicans to human buccal epithelial cells: host-induced protein synthesis and signaling events. Infect Immun. 1995 Feb;63(2):569–572. doi: 10.1128/iai.63.2.569-572.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bozzini S., Visai L., Pignatti P., Petersen T. E., Speziale P. Multiple binding sites in fibronectin and the staphylococcal fibronectin receptor. Eur J Biochem. 1992 Jul 1;207(1):327–333. doi: 10.1111/j.1432-1033.1992.tb17054.x. [DOI] [PubMed] [Google Scholar]
  3. Bullen J. J. The significance of iron in infection. Rev Infect Dis. 1981 Nov-Dec;3(6):1127–1138. doi: 10.1093/clinids/3.6.1127. [DOI] [PubMed] [Google Scholar]
  4. CAROLINE L., TASCHDJIAN C. L., KOZINN P. J., SCHADE A. L. REVERSAL OF SERUM FUNGISTASIS BY ADDITION OF IRON. J Invest Dermatol. 1964 Jun;42:415–419. doi: 10.1038/jid.1964.90. [DOI] [PubMed] [Google Scholar]
  5. Calderone R. A., Braun P. C. Adherence and receptor relationships of Candida albicans. Microbiol Rev. 1991 Mar;55(1):1–20. doi: 10.1128/mr.55.1.1-20.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Calderone R. A., Scheld W. M. Role of fibronectin in the pathogenesis of candidal infections. Rev Infect Dis. 1987 Jul-Aug;9 (Suppl 4):S400–S403. doi: 10.1093/clinids/9.supplement_4.s400. [DOI] [PubMed] [Google Scholar]
  7. Calhoun D. L., Galgiani J. N. Analysis of pH and buffer effects on flucytosine activity in broth dilution susceptibility testing of Candida albicans in two synthetic media. Antimicrob Agents Chemother. 1984 Sep;26(3):364–367. doi: 10.1128/aac.26.3.364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Caroline L., Rosner F., Kozinn P. J. Elevated serum iron, low unbound transferrin and candidiasis in acute leukemia. Blood. 1969 Oct;34(4):441–451. [PubMed] [Google Scholar]
  9. EAGLE H. Experimental approach to the problem of treatment failure with penicillin. I. Group A streptococcal infection in mice. Am J Med. 1952 Oct;13(4):389–399. doi: 10.1016/0002-9343(52)90293-3. [DOI] [PubMed] [Google Scholar]
  10. Elin R. J., Wolff S. M. The role of iron in nonspecific resistance to infection induced by endotoxin. J Immunol. 1974 Feb;112(2):737–745. [PubMed] [Google Scholar]
  11. Esterly N. B., Brammer S. R., Crounse R. G. The relationship of transferrin and iron to serum inhibition of Candida albicans. J Invest Dermatol. 1967 Nov;49(5):437–442. [PubMed] [Google Scholar]
  12. Filler S. G., Swerdloff J. N., Hobbs C., Luckett P. M. Penetration and damage of endothelial cells by Candida albicans. Infect Immun. 1995 Mar;63(3):976–983. doi: 10.1128/iai.63.3.976-983.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Hostetter M. K. Adhesins and ligands involved in the interaction of Candida spp. with epithelial and endothelial surfaces. Clin Microbiol Rev. 1994 Jan;7(1):29–42. doi: 10.1128/cmr.7.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. King R. D., Khan H. A., Foye J. C., Greenberg J. H., Jones H. E. Transferrin, iron, and dermatophytes. I. Serum dematophyte inhibitory component definitively identified as unsaturated transferrin. J Lab Clin Med. 1975 Aug;86(2):204–212. [PubMed] [Google Scholar]
  16. Kirby W. M. BACTERIOSTATIC AND LYTIC ACTIONS OF PENICILLIN ON SENSITIVE AND RESISTANT STAPHYLOCOCCI. J Clin Invest. 1945 Mar;24(2):165–169. doi: 10.1172/JCI101593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Klotz S. A., Hein R. C., Smith R. L., Rouse J. B. The fibronectin adhesin of Candida albicans. Infect Immun. 1994 Oct;62(10):4679–4681. doi: 10.1128/iai.62.10.4679-4681.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klotz S. A. Plasma and extracellular matrix proteins mediate in the fate of Candida albicans in the human host. Med Hypotheses. 1994 May;42(5):328–334. doi: 10.1016/0306-9877(94)90008-6. [DOI] [PubMed] [Google Scholar]
  19. Klotz S. A., Smith R. L. A fibronectin receptor on Candida albicans mediates adherence of the fungus to extracellular matrix. J Infect Dis. 1991 Mar;163(3):604–610. doi: 10.1093/infdis/163.3.604. [DOI] [PubMed] [Google Scholar]
  20. Klotz S. A., Smith R. L. Gelatin fragments block adherence of Candida albicans to extracellular matrix proteins. Microbiology. 1995 Oct;141(Pt 10):2681–2684. doi: 10.1099/13500872-141-10-2681. [DOI] [PubMed] [Google Scholar]
  21. Manns J. M., Mosser D. M., Buckley H. R. Production of a hemolytic factor by Candida albicans. Infect Immun. 1994 Nov;62(11):5154–5156. doi: 10.1128/iai.62.11.5154-5156.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Minagawa H., Kitaura K., Nakamizo N. Effects of pH on the activity of ketoconazole against Candida albicans. Antimicrob Agents Chemother. 1983 Jan;23(1):105–107. doi: 10.1128/aac.23.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Munjal I. D., Crawford D. R., Blake D. A., Sabet M. D., Gordon S. R. Thrombospondin: biosynthesis, distribution, and changes associated with wound repair in corneal endothelium. Eur J Cell Biol. 1990 Aug;52(2):252–263. [PubMed] [Google Scholar]
  24. Nègre E., Vogel T., Levanon A., Guy R., Walsh T. J., Roberts D. D. The collagen binding domain of fibronectin contains a high affinity binding site for Candida albicans. J Biol Chem. 1994 Sep 2;269(35):22039–22045. [PubMed] [Google Scholar]
  25. Payne S. M., Finkelstein R. A. The critical role of iron in host-bacterial interactions. J Clin Invest. 1978 Jun;61(6):1428–1440. doi: 10.1172/JCI109062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pendrak M. L., Klotz S. A. Adherence of Candida albicans to host cells. FEMS Microbiol Lett. 1995 Jun 15;129(2-3):103–113. doi: 10.1111/j.1574-6968.1995.tb07566.x. [DOI] [PubMed] [Google Scholar]
  27. Penn C., Klotz S. A. Binding of plasma fibronectin to Candida albicans occurs through the cell binding domain. Microb Pathog. 1994 Dec;17(6):387–393. doi: 10.1006/mpat.1994.1084. [DOI] [PubMed] [Google Scholar]
  28. Roberts D. D., Rao C. N., Magnani J. L., Spitalnik S. L., Liotta L. A., Ginsburg V. Laminin binds specifically to sulfated glycolipids. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1306–1310. doi: 10.1073/pnas.82.5.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rostagno A. A., Frangione B., Gold L. Biochemical studies on the interaction of fibronectin with Ig. J Immunol. 1991 Apr 15;146(8):2687–2693. [PubMed] [Google Scholar]
  30. Santoni G., Gismondi A., Liu J. H., Punturieri A., Santoni A., Frati L., Piccoli M., Djeu J. Y. Candida albicans expresses a fibronectin receptor antigenically related to alpha 5 beta 1 integrin. Microbiology. 1994 Nov;140(Pt 11):2971–2979. doi: 10.1099/13500872-140-11-2971. [DOI] [PubMed] [Google Scholar]
  31. Sela S., Aviv A., Tovi A., Burstein I., Caparon M. G., Hanski E. Protein F: an adhesin of Streptococcus pyogenes binds fibronectin via two distinct domains. Mol Microbiol. 1993 Dec;10(5):1049–1055. doi: 10.1111/j.1365-2958.1993.tb00975.x. [DOI] [PubMed] [Google Scholar]
  32. Weinberg E. D. Iron and infection. Microbiol Rev. 1978 Mar;42(1):45–66. doi: 10.1128/mr.42.1.45-66.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yamada K. M. Adhesive recognition sequences. J Biol Chem. 1991 Jul 15;266(20):12809–12812. [PubMed] [Google Scholar]

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

RESOURCES