Section of Infection Biology, Department of Functional Bioscience, Fukuoka Dental College, Japan.
Biol Pharm Bull. 2012;35(8):1371-3. doi: 10.1248/bpb.b12-00228.
Elevation in the temperature induces heat stress to both host cells and the invading pathogen. This study aimed to determine whether continuous mild heat stress (increased temperature without causing significant damage to host cells) can increase susceptibility of biofilm formation of the opportunistic fungal pathogen Candida albicans to low concentrations of three typical antifungal agents. In this way the side effects associated with higher concentrations of the antifungal agents on host cells would be reduced. Fluconazole and micafungin at concentrations ranging from 0.0625 to 2 µg/mL and amphotericin B at concentrations ranging from 0.0625 to 1 µg/mL inhibited less than 20% of cells in biofilm formation. Biofilm formation at 39 or 41°C compared to 37°C resulted in increased susceptibility to the three agents, but especially micafungin. These data suggest that mild heat stress (39°C) would be valuable for increasing the effectiveness of low concentrations of antifungal agents against C. albicans biofilm formation. Thus, the concept of continuous mild heat stress at the site of insertion of medical devices or catheters combined with antifungal agents could be beneficial.
温度升高会给宿主细胞和入侵病原体都带来热应激。本研究旨在确定持续的轻度热应激(在不导致宿主细胞明显损伤的情况下提高温度)是否会增加机会性真菌病原体白色念珠菌对三种典型抗真菌药物低浓度的生物膜形成的易感性。这样,就可以降低与宿主细胞更高浓度的抗真菌药物相关的副作用。氟康唑和米卡芬净在 0.0625 至 2μg/ml 的浓度范围内,两性霉素 B 在 0.0625 至 1μg/ml 的浓度范围内,对生物膜形成的细胞抑制率均低于 20%。与 37°C 相比,39°C 或 41°C 的生物膜形成导致对三种药物的敏感性增加,尤其是米卡芬净。这些数据表明,轻度热应激(39°C)可提高低浓度抗真菌药物对白色念珠菌生物膜形成的有效性。因此,医疗器械或导管插入部位持续温和热应激与抗真菌药物联合使用的概念可能是有益的。