Abstract
An N-acetyl-D-[14C]glucosamine radiolabel incorporation assay has been used to monitor chitin biosynthesis in whole cells of Candida albicans both in vitro and in vivo in two different mouse infection models, one using the peritoneal cavity as a chamber in which to add and retrieve cells and the other using infected kidneys. Specific labeling of chitin in alkali-insoluble material was confirmed by chitinase digestion, analysis of acid hydrolysates, and the use of nikkomycin Z as a probe. Nikkomycin Z was shown to strongly inhibit chitin biosynthesis in C. albicans grown in vitro and in vivo in both models. This demonstrates that nikkomycin Z-susceptible chitin synthase activity is present in C. albicans when the fungus is in its pathogenic state in vivo. The limited use of nikkomycin as a therapeutic agent is discussed.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Au-Young J., Robbins P. W. Isolation of a chitin synthase gene (CHS1) from Candida albicans by expression in Saccharomyces cerevisiae. Mol Microbiol. 1990 Feb;4(2):197–207. doi: 10.1111/j.1365-2958.1990.tb00587.x. [DOI] [PubMed] [Google Scholar]
- Becker J. M., Covert N. L., Shenbagamurthi P., Steinfeld A. S., Naider F. Polyoxin D inhibits growth of zoopathogenic fungi. Antimicrob Agents Chemother. 1983 Jun;23(6):926–929. doi: 10.1128/aac.23.6.926. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Becker J. M., Marcus S., Tallock J., Miller D., Krainer E., Khare R. K., Naider F. Use of the chitin-synthesis inhibitor nikkomycin to treat disseminated candidiasis in mice. J Infect Dis. 1988 Jan;157(1):212–214. doi: 10.1093/infdis/157.1.212. [DOI] [PubMed] [Google Scholar]
- Braun P. C., Calderone R. A. Chitin synthesis in Candida albicans: comparison of yeast and hyphal forms. J Bacteriol. 1978 Mar;133(3):1472–1477. doi: 10.1128/jb.133.3.1472-1477.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buffo J., Herman M. A., Soll D. R. A characterization of pH-regulated dimorphism in Candida albicans. Mycopathologia. 1984 Mar 15;85(1-2):21–30. doi: 10.1007/BF00436698. [DOI] [PubMed] [Google Scholar]
- Cabib E. Differential inhibition of chitin synthetases 1 and 2 from Saccharomyces cerevisiae by polyoxin D and nikkomycins. Antimicrob Agents Chemother. 1991 Jan;35(1):170–173. doi: 10.1128/aac.35.1.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cabib E., Sburlati A., Bowers B., Silverman S. J. Chitin synthase 1, an auxiliary enzyme for chitin synthesis in Saccharomyces cerevisiae. J Cell Biol. 1989 May;108(5):1665–1672. doi: 10.1083/jcb.108.5.1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cassone A. Cell wall of Candida albicans: its functions and its impact on the host. Curr Top Med Mycol. 1989;3:248–314. doi: 10.1007/978-1-4612-3624-5_10. [DOI] [PubMed] [Google Scholar]
- Cassone A. Cell wall of pathogenic yeasts and implications for antimycotic therapy. Drugs Exp Clin Res. 1986;12(6-7):635–643. [PubMed] [Google Scholar]
- Chattaway F. W., Holmes M. R., Barlow A. J. Cell wall composition of the mycelial and blastospore forms of Candida albicans. J Gen Microbiol. 1968 May;51(3):367–376. doi: 10.1099/00221287-51-3-367. [DOI] [PubMed] [Google Scholar]
- Chen-Wu J. L., Zwicker J., Bowen A. R., Robbins P. W. Expression of chitin synthase genes during yeast and hyphal growth phases of Candida albicans. Mol Microbiol. 1992 Feb;6(4):497–502. doi: 10.1111/j.1365-2958.1992.tb01494.x. [DOI] [PubMed] [Google Scholar]
- Chiew Y. Y., Shepherd M. G., Sullivan P. A. Regulation of chitin synthesis during germ-tube formation in Candida albicans. Arch Microbiol. 1980 Mar;125(1-2):97–104. doi: 10.1007/BF00403204. [DOI] [PubMed] [Google Scholar]
- Hector R. F., Braun P. C., Hart J. T., Kamarck M. E. The use of flow cytometry to monitor chitin synthesis in regenerating protoplasts of Candida albicans. J Med Vet Mycol. 1990;28(1):51–57. doi: 10.1080/02681219080000071. [DOI] [PubMed] [Google Scholar]
- Hector R. F., Braun P. C. Synergistic action of nikkomycins X and Z with papulacandin B on whole cells and regenerating protoplasts of Candida albicans. Antimicrob Agents Chemother. 1986 Mar;29(3):389–394. doi: 10.1128/aac.29.3.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hector R. F., Zimmer B. L., Pappagianis D. Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis. Antimicrob Agents Chemother. 1990 Apr;34(4):587–593. doi: 10.1128/aac.34.4.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee K. L., Buckley H. R., Campbell C. C. An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida Albicans. Sabouraudia. 1975 Jul;13(2):148–153. doi: 10.1080/00362177585190271. [DOI] [PubMed] [Google Scholar]
- Lehmann P. F., White L. O. Chitin assay used to demonstrate renal localization and cortisone-enhanced growth of Aspergillus fumigatus mycelium in mice. Infect Immun. 1975 Nov;12(5):987–992. doi: 10.1128/iai.12.5.987-992.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Naider F., Becker J. M. Peptide transport in Candida albicans: implications for the development of antifungal agents. Curr Top Med Mycol. 1988;2:170–198. doi: 10.1007/978-1-4612-3730-3_5. [DOI] [PubMed] [Google Scholar]
- Shaw J. A., Mol P. C., Bowers B., Silverman S. J., Valdivieso M. H., Durán A., Cabib E. The function of chitin synthases 2 and 3 in the Saccharomyces cerevisiae cell cycle. J Cell Biol. 1991 Jul;114(1):111–123. doi: 10.1083/jcb.114.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sullivan P. A., Yin C. Y., Molloy C., Templeton M. D., Shepherd M. G. An analysis of the metabolism and cell wall composition of Candida albicans during germ-tube formation. Can J Microbiol. 1983 Nov;29(11):1514–1525. doi: 10.1139/m83-233. [DOI] [PubMed] [Google Scholar]
- Van den Bossche H., Willemsens G., Cools W., Cornelissen F., Lauwers W. F., van Cutsem J. M. In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis. Antimicrob Agents Chemother. 1980 Jun;17(6):922–928. doi: 10.1128/aac.17.6.922. [DOI] [PMC free article] [PubMed] [Google Scholar]
