In Vitro Analyses of Mild Heat Stress in Combination with Antifungal Agents against Aspergillus fumigatus Biofilm
In Vitro Analyses of Mild Heat Stress in Combination with Antifungal Agents against Aspergillus fumigatus Biofilm
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DOI：
10.1128/aac.01007-13
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发表时间：
2013-12
影响因子：
4.9
通讯作者：
R. Zeng;Min Li;Qing Chen;Le Wang;P. Zhan;Chong Wang;G. Lv;Yong-nian Shen;Weida Liu
中科院分区：
文献类型：
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作者：
R. Zeng;Min Li;Qing Chen;Le Wang;P. Zhan;Chong Wang;G. Lv;Yong-nian Shen;Weida Liu
摘要 烟曲霉生物膜仍然对临床环境中的有效治疗提出挑战。虽然轻度热应激已被引入作为传染病的治疗方法，但轻度热应激对烟曲霉生物膜形成和抗真菌敏感性的有效性仍不清楚。在本研究中，使用共焦激光扫描显微镜（CLSM）对三种不同的连续轻度热应激方案（37°C、39°C 和 41°C）下烟曲霉生物膜的形成进行成像和量化。此外，在上述条件下结合抗真菌药物（两性霉素 B [AMB]、米卡芬净 [MCF] 和伏立康唑 [VOC]）在早期和晚期研究了真菌生长。 CLSM 分析表明，较高的温度会导致更早的发芽和更大的菌丝伸长，但极性生长较差并减少生物膜厚度。在生物膜形成的早期阶段，在39°C或41°C下与MCF或VOC联合处理与在37°C下使用相同药物的类似处理在生物量形成方面没有产生明显差异。有趣的是，37°C 下的 AMB 处理比 39°C 和 41°C 下的处理抑制早期生物膜形成的程度要大得多。在生物膜形成的后期，与 37°C 相比，使用 AMB、MCF 和 VOC 在 39 和 41°C 进行温和热处理抑制了生物质形成。目前的数据表明，轻度热应激对体外生物膜形成具有负调节作用，在生物膜形成后期通过轻度热处理改进抗真菌药物，为曲霉病临床管理的可能有效策略提供了有用的指示。
ABSTRACT Aspergillus fumigatus biofilms still present a challenge for effective treatment in clinical settings. While mild heat stress has been introduced as a treatment for infectious diseases, the effectiveness of mild heat stress on A. fumigatus biofilm formation and antifungal susceptibility is still unknown. In the present study, confocal laser scanning microscopy (CLSM) was used to image and quantify Aspergillus fumigatus biofilm formation under three different regimens of continuous mild heat stress: at 37, 39, and 41°C. Furthermore, fungal growth has been investigated under the above conditions in combination with antifungal drugs (amphotericin B [AMB], micafungin [MCF], and voriconazole [VOC]) at early and late stages. CLSM analysis showed that higher temperatures induce earlier germination and greater hyphal elongation but poorer polar growth and reduced biofilm thickness. In the early stage of biofilm formation, the combination of treatment at 39 or 41°C with MCF or VOC produced no visible difference in biomass formation from similar treatments at 37°C with the same drug. Interestingly, AMB treatment at 37°C inhibited early stage biofilm formation to a much greater extent than at 39 and 41°C. At the late stage of biofilm formation, the mild heat treatments at 39 and 41°C with AMB, MCF, and VOC inhibited biomass formation compared to that at 37°C. The present data show that mild heat stress has a negative regulatory effect on biofilm formation in vitro, and antifungal drug improvement with mild heat treatment at late-stage biofilm formation provides useful indications of possible effective strategies for clinical management of aspergillosis.