Department of Bioclinical Sciences, Health Sciences Center, Kuwait University, Safat, Kuwait.
Mycoses. 2013 Jul;56(4):463-70. doi: 10.1111/myc.12059. Epub 2013 Feb 14.
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 1 h. 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.
黏附被认为是口腔念珠菌病发病机制的初始过程。假丝酵母的芽管及其相对细胞表面疏水性（CSH）是促成因素。目前已证明杜氏念珠菌是一种与复发性口腔念珠菌病有关的机会致病菌。口腔念珠菌病可以用多烯类和唑类抗真菌药物治疗，如两性霉素 B、酮康唑和氟康唑。然而，由于唾液的稀释作用和口腔肌肉的清洁作用，这些药物在口腔内的浓度会波动并降至治疗剂量以下。因此，口腔内的致病性酵母可能会短暂接触到抗真菌药物。本研究旨在探讨短暂接触亚致死浓度这些抗真菌药物对杜氏念珠菌芽管形成和 CSH 的影响。确定药物的最低抑菌浓度后，将 20 株口腔分离的杜氏念珠菌暴露于这些抗真菌药物的亚致死浓度下 1 小时。短暂接触后，去除药物，随后在芽管诱导培养基中孵育，并暴露于双相烃测定法中，分别定量这些分离物的芽管形成和 CSH。与对照组相比，两性霉素 B 暴露几乎完全抑制了芽管形成的能力，平均百分比降低 95.91%（P<0.0001），而酮康唑和氟康唑也显著抑制了芽管形成，但程度较小，平均百分比降低分别为 18.73%和 12.01%（P<0.05）。与对照组相比，两性霉素 B 和酮康唑暴露均显著抑制 CSH，平均百分比降低分别为 33.09%和 21.42%（P<0.001），而氟康唑暴露对 CSH 无显著抑制作用（9.21%；P>0.05）。从临床角度来看，即使是短暂接触这些药物的亚致死浓度，这种情况在口腔环境中也很常见，但通过抑制杜氏念珠菌的致病性，仍会继续发挥抗真菌作用。
