Oxidative Stress Response Tips the Balance in Aspergillus terreus Amphotericin B Resistance
Oxidative Stress Response Tips the Balance in Aspergillus terreus Amphotericin B Resistance
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DOI：
10.1128/aac.00670-17
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发表时间：
2017-10-01
影响因子：
4.9
通讯作者：
Wilflingseder, Doris
中科院分区：
文献类型：
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作者：
Jukic, Emina;Blatzer, Michael;Wilflingseder, Doris
在这项研究中，我们描述了抗氧化酶对两性霉素B （AmB）耐药（ATR）和罕见的AmB敏感（ATS）临床土曲霉分离株的影响。我们研究了在AmB处理条件下，ATS和ATR菌株中超氧化物歧化酶（SOD）和过氧化氢酶（CAT）编码基因的表达谱、SOD的酶活性、超氧化物阴离子的产生和参与氧化应激反应（OSR）的信号通路。我们发现，与ATS菌株相比，ATR菌株具有几乎两倍的基础SOD活性，并且ATR菌株表现出增强的OSR，在AmB处理后，ATR菌株的sod2 mRNA水平显著升高，cat转录本显著增加。特别是，SOD和CAT蛋白的抑制使耐药分离物在体外对药物相当敏感。综上所述，本研究表明，sod和cat在土拟鸡AmB耐药中起着至关重要的作用，针对OSR可能为耐药物种的治疗提供新的思路。
In this study, we characterize the impact of antioxidative enzymes in amphotericin B (AmB)-resistant (ATR) and rare AmB-susceptible (ATS) clinical Aspergillus terreus isolates. We elucidate expression profiles of superoxide dismutase (SOD) and catalase (CAT)-encoding genes, enzymatic activities of SODs, and superoxide anion production and signaling pathways involved in the oxidative stress response (OSR) in ATS and ATR strains under AmB treatment conditions. We show that ATR strains possess almost doubled basal SOD activity compared to that of ATS strains and that ATR strains exhibit an enhanced OSR, with significantly higher sod2 mRNA levels and significantly increased cat transcripts in ATR strains upon AmB treatment. In particular, inhibition of SOD and CAT proteins renders resistant isolates considerably susceptible to the drug in vitro. In conclusion, this study shows that SODs and CATs are crucial for AmB resistance in A. terreus and that targeting the OSR might offer new treatment perspectives for resistant species.