Inhibitory and morphological effects of several antifungal agents on three types of Candida albicans morphological mutants.
The susceptibilities to several antifungal agents of three classes of Candida albicans morphological mutants were studied. Also investigated were the morphological effects of these drugs, at sub-inhibitory concentrations. An F- strain (1001-92'), unable to produce mycelium, proved to be significantly more sensitive to ketoconazole when compared with the wild-type. A mutant representative of a second class, namely 1001 FR, that grew permanently as filamentous pseudomycelial structures, showed susceptibilities similar to those of the wild-type. Strains NEL102 and NEL103 belonged to a third class of mutants whose blastospores gave rise to filamentous hypha-type structures in the absence of any inducer. These strains were somewhat more sensitive to amphotericin B, fluconazole and miconazole than the wild-type. 5-Fluorocytosine caused a pronounced bending of the filamentous structures, whereas amphotericin B prevented filamentous growth. In the presence of the azole antifungals the cells appeared as aggregates or chains of swollen structures, many of them with a bud-like formation. The effect of cilofungin in preventing the formation of regular filamentous structures was even more pronounced. Under conditions of germ tube formation, NEL102 proved to be significantly more sensitive to cilofungin than in nutrient medium, in contrast with its response to ketoconazole and fluconazole which only inhibited this strain at concentrations much higher than in nutrient medium. The cilofungin sensitive function(s) of NEL102 could be over-expressed in Lee's medium, leading to an enhanced sensitivity to the drug that was less marked in the wild-type strain.
Departamento de Microbiolgía II, Facultad de Farmacia, Universidad Complutense, Madrid, Spain.
C
C
Gil
R
R
Pérez-Diaz
C
C
Nombela
D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D054714:Echinocandins; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000187:drug effects / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011090:Polyenes / Q000494:pharmacology
D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D010456:Peptides, Cyclic; D011090:Polyenes; C042101:cilofungin