School of Life Sciences, SRTM University, Nanded, MS 431606, India.
Braz J Infect Dis. 2013 Jul-Aug;17(4):395-400. doi: 10.1016/j.bjid.2012.11.002. Epub 2013 Apr 18.
Biofilms formed by Candida albicans, a human pathogen, are known to be resistant to different antifungal agents. Novel strategies to combat the biofilm associated Candida infections like multiple drug therapy are being explored. In this study, potential of chloroquine to be a partner drug in combination with four antifungal agents, namely fluconazole, voriconazole, amphotericin B, and caspofungin, was explored against biofilms of C. albicans. Activity of various concentrations of chloroquine in combination with a particular antifungal drug was analyzed in a checkerboard format. Growth of biofilm in presence of drugs was analyzed by XTT-assay, in terms of relative metabolic activity compared to that of drug free control. Results obtained by XTT-metabolic assay were confirmed by scanning electron microscopy. The interactions between chloroquine and four antifungal drugs were determined by calculating fractional inhibitory concentration indices. Azole resistance in biofilms was reverted significantly (p<0.05) in presence of 250μg/mL of chloroquine, which resulted in inhibition of biofilms at very low concentrations of antifungal drugs. No significant alteration in the sensitivity of biofilms to caspofungin and amphotericin B was evident in combination with chloroquine. This study for the first time indicates that chloroquine potentiates anti-biofilm activity of fluconazole and voriconazole.
由人类病原体白色念珠菌形成的生物膜已知对不同的抗真菌药物具有抗性。正在探索新的策略来对抗生物膜相关的念珠菌感染,如多药物治疗。在这项研究中,探索了氯喹作为与四种抗真菌药物(氟康唑、伏立康唑、两性霉素 B 和卡泊芬净)联合使用的潜在伙伴药物,以对抗白色念珠菌的生物膜。以棋盘格式分析了不同浓度的氯喹与特定抗真菌药物联合使用的活性。通过 XTT 测定法分析了药物存在下生物膜的生长,相对于无药物对照,生物膜的相对代谢活性。通过扫描电子显微镜确认了 XTT 代谢测定法获得的结果。通过计算部分抑制浓度指数确定了氯喹与四种抗真菌药物之间的相互作用。在 250μg/mL 氯喹的存在下,生物膜中的唑类耐药性显著(p<0.05)逆转,这导致在非常低浓度的抗真菌药物下抑制了生物膜。与氯喹联合使用时,生物膜对卡泊芬净和两性霉素 B 的敏感性没有明显改变。这项研究首次表明,氯喹增强了氟康唑和伏立康唑的抗生物膜活性。