Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1992 Oct;36(10):2239–2244. doi: 10.1128/aac.36.10.2239

Modulation of interactions of Candida albicans and endothelial cells by fluconazole and amphotericin B.

M A Ghannoum 1, S G Filler 1, A S Ibrahim 1, Y Fu 1, J E Edwards Jr 1
PMCID: PMC245483  PMID: 1444305

Abstract

Using an in vitro model of intravascular infection, we examined the effects of exposure to subinhibitory concentrations of fluconazole and amphotericin B on the ability of Candida albicans to adhere to and damage human umbilical vein endothelial cells. Incubation of the organisms for 18 h in 0.5x the MICs of fluconazole and amphotericin B inhibited endothelial cell adherence by 22 and 91%, respectively (P less than 0.001 for each drug). Candida-induced endothelial cell injury was also decreased by exposing the organisms to the antifungal drugs while in contact with the endothelial cells. Fluconazole inhibited damage by approximately 50% at concentrations ranging from 0.25x to 5x the MIC (P less than 0.01 for each concentration). Exposure to amphotericin B at 0.5x the MIC completely blocked the ability of the organisms to injure endothelial cells. The capacities of the antifungal agents to inhibit endothelial cell injury paralleled their abilities to suppress candidal germination. Organisms exposed to up to 5x the MIC of fluconazole had diminished, but still detectable, germ tube production and elongation, whereas incubation in 0.5x the MIC of amphotericin B completely abrogated germination. In addition to their direct effects on the growth of C. albicans, fluconazole and amphotericin B may decrease the ability of the fungus to disseminate hematogenously by inhibiting the organisms' capacity to adhere to and injure endothelial cells.

Full text

PDF
2239

Images in this article

2241Image
on p.2241

Selected References

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

  1. Abu-el Teen K., Ghannum M., Stretton R. J. Effects of sub-inhibitory concentrations of antifungal agents on adherence of Candida spp. to buccal epithelial cells in vitro. Mycoses. 1989 Nov;32(11):551–562. doi: 10.1111/j.1439-0507.1989.tb02180.x. [DOI] [PubMed] [Google Scholar]
  2. Anderson M. L., Odds F. C. Adherence of Candida albicans to vaginal epithelia: significance of morphological form and effect of ketoconazole. Mykosen. 1985 Nov;28(11):531–540. doi: 10.1111/j.1439-0507.1985.tb02083.x. [DOI] [PubMed] [Google Scholar]
  3. Cutler J. E. Putative virulence factors of Candida albicans. Annu Rev Microbiol. 1991;45:187–218. doi: 10.1146/annurev.mi.45.100191.001155. [DOI] [PubMed] [Google Scholar]
  4. Darwazeh A. M., Lamey P. J., Lewis M. A., Samaranayake L. P. Systemic fluconazole therapy and in vitro adhesion of Candida albicans to human buccal epithelial cells. J Oral Pathol Med. 1991 Jan;20(1):17–19. doi: 10.1111/j.1600-0714.1991.tb00881.x. [DOI] [PubMed] [Google Scholar]
  5. Edwards J. E., Jr, Rotrosen D., Fontaine J. W., Haudenschild C. C., Diamond R. D. Neutrophil-mediated protection of cultured human vascular endothelial cells from damage by growing Candida albicans hyphae. Blood. 1987 May;69(5):1450–1457. [PubMed] [Google Scholar]
  6. Filler S. G., Ibe B. O., Luckett P. M., Raj J. U., Edwards J. E., Jr Candida albicans stimulates endothelial cell eicosanoid production. J Infect Dis. 1991 Nov;164(5):928–935. doi: 10.1093/infdis/164.5.928. [DOI] [PubMed] [Google Scholar]
  7. Ham E. A., Soderman D. D., Zanetti M. E., Dougherty H. W., McCauley E., Kuehl F. A., Jr Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4349–4353. doi: 10.1073/pnas.80.14.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hughes C. E., Bennett R. L., Tuna I. C., Beggs W. H. Activities of fluconazole (UK 49,858) and ketoconazole against ketoconazole-susceptible and -resistant Candida albicans. Antimicrob Agents Chemother. 1988 Feb;32(2):209–212. doi: 10.1128/aac.32.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Johnson E. M., Warnock D. W., Richardson M. D., Douglas C. J. In-vitro effect of itraconazole, ketoconazole and amphotericin B on the phagocytic and candidacidal function of human neutrophils. J Antimicrob Chemother. 1986 Jul;18(1):83–91. doi: 10.1093/jac/18.1.83. [DOI] [PubMed] [Google Scholar]
  10. Liss R. H., Letourneau R. J. Fungispecificity of fluconazole against Candida albicans. Mycopathologia. 1989 Dec;108(3):173–178. doi: 10.1007/BF00436222. [DOI] [PubMed] [Google Scholar]
  11. Mehentee J. F., Hay R. J. Effect of antifungal agents on the adherence of Candida albicans to murine gastrointestinal mucosal surfaces. J Antimicrob Chemother. 1990 Jan;25(1):111–119. doi: 10.1093/jac/25.1.111. [DOI] [PubMed] [Google Scholar]
  12. Nugent K. M., Couchot K. R. Effects of sublethal concentrations of amphotericin B on Candida albicans. J Infect Dis. 1986 Oct;154(4):665–669. doi: 10.1093/infdis/154.4.665. [DOI] [PubMed] [Google Scholar]
  13. Nugent K. M., Couchot K. R., Gray L. D. Effect of Candida morphology on amphotericin B susceptibility. Antimicrob Agents Chemother. 1987 Feb;31(2):335–336. doi: 10.1128/aac.31.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Odds F. C., Webster C. E. Effects of azole antifungals in vitro on host/parasite interactions relevant to Candida infections. J Antimicrob Chemother. 1988 Oct;22(4):473–481. doi: 10.1093/jac/22.4.473. [DOI] [PubMed] [Google Scholar]
  15. Perfect J. R., Granger D. L., Durack D. T. Effects of antifungal agents and gamma interferon on macrophage cytotoxicity for fungi and tumor cells. J Infect Dis. 1987 Aug;156(2):316–323. doi: 10.1093/infdis/156.2.316. [DOI] [PubMed] [Google Scholar]
  16. Pfaller M. A., Rinaldi M. G., Galgiani J. N., Bartlett M. S., Body B. A., Espinel-Ingroff A., Fromtling R. A., Hall G. S., Hughes C. E., Odds F. C. Collaborative investigation of variables in susceptibility testing of yeasts. Antimicrob Agents Chemother. 1990 Sep;34(9):1648–1654. doi: 10.1128/aac.34.9.1648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rotrosen D., Edwards J. E., Jr, Gibson T. R., Moore J. C., Cohen A. H., Green I. Adherence of Candida to cultured vascular endothelial cells: mechanisms of attachment and endothelial cell penetration. J Infect Dis. 1985 Dec;152(6):1264–1274. doi: 10.1093/infdis/152.6.1264. [DOI] [PubMed] [Google Scholar]
  18. Sullivan G. W., Carper H. T., Mandell G. L. Pentoxifylline modulates activation of human neutrophils by amphotericin B in vitro. Antimicrob Agents Chemother. 1992 Feb;36(2):408–416. doi: 10.1128/aac.36.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Troke P. F., Andrews R. J., Brammer K. W., Marriott M. S., Richardson K. Efficacy of UK-49,858 (fluconazole) against Candida albicans experimental infections in mice. Antimicrob Agents Chemother. 1985 Dec;28(6):815–818. doi: 10.1128/aac.28.6.815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Van 't Wout J. W., Meynaar I., Linde I., Poell R., Mattie H., Van Furth R. Effect of amphotericin B, fluconazole and itraconazole on intracellular Candida albicans and germ tube development in macrophages. J Antimicrob Chemother. 1990 May;25(5):803–811. doi: 10.1093/jac/25.5.803. [DOI] [PubMed] [Google Scholar]
  21. Van t Wout J. W., Mattie H., van Furth R. Comparison of the efficacies of amphotericin B, fluconazole, and itraconazole against a systemic Candida albicans infection in normal and neutropenic mice. Antimicrob Agents Chemother. 1989 Feb;33(2):147–151. doi: 10.1128/aac.33.2.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vuddhakul V., McCormack J. G., Seow W. K., Smith S. E., Thong Y. H. Inhibition of adherence of Candida albicans by conventional and experimental antifungal drugs. J Antimicrob Chemother. 1988 Jun;21(6):755–763. doi: 10.1093/jac/21.6.755. [DOI] [PubMed] [Google Scholar]
  23. Zimmerman G. A., Wiseman G. A., Hill H. R. Human endothelial cells modulate granulocyte adherence and chemotaxis. J Immunol. 1985 Mar;134(3):1866–1874. [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES