Sub-therapeutic exposure to polyene antimycotics elicits a post-antifungal effect (PAFE), and depresses the cell surface hydrophobicity of oral Candida albicans isolates

Abstract

Post-antifungal effect (PAFE) is defined as the suppression of growth that persists following limited exposure of fungi to antimycotics and subsequent removal of the drug. The fungal pathogen Candida albicans is the major aetiologic agent of oral candidosis, and the cell surface hydrophobicity (CSH) of this yeast is considered a critical factor contributing to its colonisation potential. As the concentration of topically prescribed antifungals reach sub-therapeutic levels at dosage intervals, the study of the polyene-induced PAFE and its impact on the CSH of oral C. albicans should be of clinical relevance. Hence the aims of this investigation were to measure the PAFE and CSH of 12 isolates of C. albicans following limited exposure (1 h) to nystatin and amphotericin B and also to investigate the ultrastructural features of yeast cells following such antifungal exposure. The yeasts were exposed to sub-lethal concentrations of nystatin (x 2 MIC) and amphotericin B (x 2 MIC) for a period of 1 h. Following subsequent removal of the drug, the PAFE and the CSH of the isolates were assessed by a turbidometric measurement of growth and a biphasic aqueous-hydrocarbon assay, respectively. The mean duration of PAFE of nystatin and amphotericin B were 5.99 (±0.49) h and 8.73 (±0.93) h, respectively, while the reduction in CSH following exposure to these drugs were 17.32% (P < 0.05 for 83% of the isolates) and 14.26% (P < 0.05 for 66% of the isolates), respectively. On scanning electron microscopy the exposed cells were seen to undergo collapse of the internal cell membrane, leaving an intact cell wall, while a proportion of cells were deflated. Some cells showed intense puckering of the cell wall, resulting in a mulberry appearance. Taken together, these data elucidate additional mechanisms by which polyene antimycotics may operate in vivo to suppress candidal pathogenicity.