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Antimicrobial Agents and Chemotherapy, January 1999, p. 100-105, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Acetate-Mediated Growth Inhibition in Sterol 14alpha -Demethylation-Deficient Cells of Candida albicans

Osamu Shimokawa and Hiroaki Nakayama*

Department of Microbiology, Faculty of Dentistry, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan

Received 4 February 1998/Returned for modification 1 April 1998/Accepted 20 October 1998

Candida albicans is a fungus thought to be viable in the presence of a deficiency in sterol 14alpha -demethylation. We showed in a strain of this species that the deficiency, caused either by a mutation or by an azole antifungal agent, made the cells susceptible to growth inhibition by acetate included in the culture medium. Studies with a mutant demonstrated that the inhibition was complete at a sodium acetate concentration of 0.24 M (20 g/liter) and was evident even at a pH of 8, the latter result indicating the involvement of acetate ions rather than the undissociated form of acetic acid. In fluconazole-treated cells, sterol profiles determined by thin-layer chromatography revealed that the minimum sterol 14alpha -demethylation-inhibitory concentrations (MDICs) of the drug, thought to be the most important parameter for clinical purposes, were practically identical in the media with and without 0.24 M acetate and were equivalent to the MIC in the acetate-supplemented medium. The acetate-mediated growth inhibition of azole-treated cells was confirmed with two additional strains of C. albicans and four different agents, suggesting the possibility of generalization. From these results, it was surmised that the acetate-containing medium may find use in azole susceptibility testing, for which there is currently no method capable of measuring MDICs directly for those fungi whose viability is not lost as a result of sterol 14alpha -demethylation deficiency. Additionally, the acetate-supplemented agar medium was found to be useful in detecting reversions from sterol 14alpha -demethylation deficiency to proficiency.

* Corresponding author. Mailing address: Department of Microbiology, Faculty of Dentistry, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-6331. Fax: 81-92-642-6263. E-mail: nakhdef{at}mbox.nc.kyushu-u.ac.jp.

Antimicrobial Agents and Chemotherapy, January 1999, p. 100-105, Vol. 43, No. 1
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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