Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system.
Kinetic characterisation and inhibitor sensitivity of Candida albicans and Candida auris recombinant AOX expressed in a self-assembled proteoliposome system.
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DOI：
10.1038/s41598-021-94320-3
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发表时间：
2021-07-20
影响因子：
4.6
通讯作者：
Moore AL
中科院分区：
文献类型：
--
作者：
Copsey AC;Barsottini MRO;May B;Xu F;Albury MS;Young L;Moore AL
念珠菌引起的念珠菌病是医院环境中的严重威胁，是获得性感染和死亡的主要原因，也是导致Covid-19死亡率的可能因素。随着对杀菌剂耐药病原体的增加，念珠菌病的发病率在世界范围内一直在上升，这突出表明需要具有新型作用模式的更有效的抗真菌药物。膜结合酶替代氧化酶（AOX）促进杀菌剂耐药性，在人类中不存在，使其成为理想的治疗靶点。然而，AOX底物（泛醇-10）的亲脂性阻碍了其在生理相关条件下的动力学表征。本研究在自组装的蛋白脂质体（PL）系统中纯化并表达了来自白色念珠菌和金黄色念珠菌的重组AOXs。测定了泛醇-10的动力学参数Km和Vmax。PL系统也被用于新型AOX抑制剂的剂量-反应测定。这些信息对于未来开发新的念珠菌治疗方法至关重要。
Candidemia caused by Candida spp. is a serious threat in hospital settings being a major cause of acquired infection and death and a possible contributor to Covid-19 mortality. Candidemia incidence has been rising worldwide following increases in fungicide-resistant pathogens highlighting the need for more effective antifungal agents with novel modes of action. The membrane-bound enzyme alternative oxidase (AOX) promotes fungicide resistance and is absent in humans making it a desirable therapeutic target. However, the lipophilic nature of the AOX substrate (ubiquinol-10) has hindered its kinetic characterisation in physiologically-relevant conditions. Here, we present the purification and expression of recombinant AOXs from C. albicans and C. auris in a self-assembled proteoliposome (PL) system. Kinetic parameters (Km and Vmax) with respect to ubiquinol-10 have been determined. The PL system has also been employed in dose–response assays with novel AOX inhibitors. Such information is critical for the future development of novel treatments for Candidemia.
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影响因子：
--
作者：
Deorukhkar, Sachin C;Saini, Santosh;Mathew, Stephen
通讯作者：
Mathew, Stephen
DOI：
10.1016/j.ijantimicag.2019.08.013
发表时间：
2019-10-01
影响因子：
10.8
作者：
Kenters, Nikki;Kiernan, Martin;Voss, Andreas
通讯作者：
Voss, Andreas
影响因子：
56.3
作者：
Chow, Nancy A.;Gade, Lalitha;Litvintseva, Anastasia P.
通讯作者：
Litvintseva, Anastasia P.
影响因子：
7.1
作者：
Cortegiani A;Misseri G;Fasciana T;Giammanco A;Giarratano A;Chowdhary A
通讯作者：
Chowdhary A
影响因子：
4.1
作者：
Huh, WK;Kang, SO
通讯作者：
Kang, SO