In Vitro Efficacy of Continuous Mild Heat Stress on the Antifungal Susceptibility of Candida albicans Biofilm Formation

In Vitro Efficacy of Continuous Mild Heat Stress on the Antifungal Susceptibility of Candida albicans Biofilm Formation
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DOI:
10.1248/bpb.b12-00228
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发表时间:
2012-08-01
影响因子:
2
通讯作者:
Kaminishi, Hidenori
Kaminishi, Hidenori
中科院分区:
医学4区
文献类型:
--
作者:
Cho, Tamaki;Nagao, Jun-ichi;Kaminishi, Hidenori

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温度升高会对宿主细胞和入侵的病原体产生热应激。本研究旨在确定持续轻度热应激(升高温度而不引起宿主细胞明显损伤)是否会增加机会性真菌病原体白色念珠菌对低浓度三种典型抗真菌药物的生物膜形成敏感性。通过这种方式,与较高浓度的抗真菌药物对宿主细胞的副作用将会减少。氟康唑和米卡芬津的浓度范围为0.0625至2 μ g/mL,两性霉素B的浓度范围为0.0625至1 μ g/mL,抑制生物膜形成的细胞不到20%。与37℃相比,39℃或41℃下形成的生物膜增加了对这三种药物的敏感性,但尤其是米卡芬津。这些数据表明,轻度热应激(39℃)对于提高低浓度抗真菌剂对白色念珠菌生物膜形成的有效性是有价值的。因此,在医疗器械或导管插入部位持续轻度热应激的概念与抗真菌药物相结合可能是有益的。
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 mu g/mL and amphotericin B at concentrations ranging from 0.0625 to 1 mu g/mL inhibited less than 20% of cells in biofilm formation. Biofilm formation at 39 or 41 degrees C compared to 37 degrees C resulted in increased susceptibility to the three agents, but especially micafungin. These data suggest that mild heat stress (39 degrees 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.