Changes in germ tube formation and cell-surface hydrophobicity of oralCandida dubliniensisisolates following brief exposure to sub-cidal concentrations of polyene and azole antifungal agents

Abstract

Adherence of Candida has been implicated as the initial process in the pathogenesis of oral candidosis. Candidal germ tubes and its relative cell-surface hydrophobicity (CSH) are contributory attributes. Candida dubliniensis is currently documented as an opportunistic pathogen allied with recurrent oral candidosis. Oral candidosis can be treated with polyene and azole antifungals such as amphotericin B, ketoconazole and fluconazole. However, the intraoral concentration of these drugs fluctuates and becomes sub-therapeutic because of the diluent effect of saliva and cleansing effect of the oral musculature. Hence, intraorally, the pathogenic yeast may undergo a brief exposure to antifungal drugs. The objective of this study was to investigate the effect of brief exposure to sub-lethal concentrations of these antifungals on the germ tube formation and CSH of C. dubliniensis. After determining the minimum inhibitory concentration of the drugs, 20 oral isolates of C. dubliniensis were exposed to sub-lethal concentrations of these antifungals for 1h. Following this brief exposure, the drugs were removed, and following subsequent incubation in a germ tube inducing medium and exposure to bi-phasic hydrocarbon assay, the germ tube formation and CSH of these isolates was quantified respectively. Compared with controls, exposure to amphotericin B almost completely suppressed the ability to form germ tubes with a mean percentage reduction of 95.91% (P<0.0001), whereas ketoconazole and fluconazole also significantly inhibited germ tube formation but to a lesser degree with a mean percentage reduction of 18.73% and 12.01% respectively (P<0.05). Compared with controls, exposure to amphotericin B and ketoconazole elicited a significant suppression on CSH with a mean percentage reduction of 33.09% and 21.42%, respectively (P<0.001), whereas exposure to fluconazole did not elicit a significant suppression on CSH (9.21%; P>0.05). In clinical terms it appears that, even a short exposure to sub-lethal concentrations of these drugs, a situation all too familiar in the oral environment, would continue to exert an antifungal effect by suppressing the pathogenic potency of C. dubliniensis.