The Elevated Endogenous Reactive Oxygen Species Contribute to the Sensitivity of the Amphotericin B-Resistant Isolate of Aspergillus flavus to Triazoles and Echinocandins.
The Elevated Endogenous Reactive Oxygen Species Contribute to the Sensitivity of the Amphotericin B-Resistant Isolate of Aspergillus flavus to Triazoles and Echinocandins.
复制标题
升高的内源性活性氧物种有助于两性霉素B-抗曲霉对三唑和棘齿蛋白的抗性分离物的敏感性。
DOI：
10.3389/fmicb.2021.680749
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发表时间：
2021
影响因子：
5.2
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Liang T;Chen W;Yang X;Wang Q;Wan Z;Li R;Liu W
黄曲霉经常被报道为侵袭性曲霉病（IA）的第二原因，以及在某些热带国家的主要原因。两性霉素B （AMB）是包括侵袭性曲霉病在内的一系列侵袭性真菌感染的临床重要治疗选择，体外对AMB的耐药性与接受AMB治疗的IA患者预后不良相关。与AMB敏感菌株相比，AMB耐药菌株AMB诱导的内源活性氧（ROS）水平较低，这是导致AMB耐药的重要原因。在本研究中，我们获得了一株抗AMB的黄曲霉菌株，其AMB MIC为32 μg/mL，对三唑类和棘白菌素敏感。该菌株的内源ROS水平升高，这强烈表明amb诱导的内源ROS降低对amb抗性没有贡献，这与在A. terreus中观察到的情况相反。此外，我们证实了内源性ROS的升高有助于抗amb的A. flavus分离物对三唑和棘白菌素的敏感性。黄曲霉内源ROS升高的原因和对AMB的抗性机制有待进一步研究。
Aspergillus flavus has been frequently reported as the second cause of invasive aspergillosis (IA), as well as the leading cause in certain tropical countries. Amphotericin B (AMB) is a clinically important therapy option for a range of invasive fungal infections including invasive aspergillosis, and in vitro resistance to AMB was associated with poor outcomes in IA patients treated with AMB. Compared with the AMB-susceptible isolates of A. terreus, the AMB-resistant isolates of A. terreus showed a lower level of AMB-induced endogenous reactive oxygen species (ROS), which was an important cause of AMB resistance. In this study, we obtained one AMB-resistant isolate of A. flavus, with an AMB MIC of 32 μg/mL, which was sensitive to triazoles and echinocandins. This isolate presented elevated endogenous ROS levels, which strongly suggested that no contribution of decreased AMB-induced endogenous ROS for AMB-resistance, opposite to those observed in A. terreus. Further, we confirmed that the elevated endogenous ROS contributed to the sensitivity of the AMB-resistant A. flavus isolate to triazoles and echinocandins. Further investigation is needed to elucidate the causes of elevated endogenous ROS and the resistance mechanism to AMB in A. flavus.
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