Photoinactivation of Catalase Sensitizes Candida albicans and Candida auris to ROS-Producing Agents and Immune Cells.
Photoinactivation of Catalase Sensitizes Candida albicans and Candida auris to ROS-Producing Agents and Immune Cells.
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DOI：
10.1002/advs.202104384
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Cheng JX
中科院分区：
文献类型：
--
作者：
Dong PT;Zhan Y;Jusuf S;Hui J;Dagher Z;Mansour MK;Cheng JX
微生物已经开发出自己的特定策略来科普活性氧（ROS）。过氧化氢酶是一种在多种需氧真菌中表达的含血红素的四聚体，在降解过氧化氢（H2O2）以促进真菌存活和宿主入侵方面表现出显着的效率。在这里，它表明，过氧化氢酶失活的蓝光使真菌细胞非常容易受到ROS的攻击。为了证实过氧化氢酶是蓝光的主要分子靶标，将野生型白色念珠菌与过氧化氢酶缺陷型突变株在410 nm处理下对ROS的敏感性进行了系统比较。在测试了广泛的真菌物种后，发现细胞内过氧化氢酶可以被410 nm蓝光有效地和普遍地灭活。还发现过氧化氢酶与ROS产生剂组合的光灭活在完全根除各种真菌物种中非常有效，包括多种耳念珠菌菌株，其为全球真菌流行病的病原体。此外，过氧化氢酶的光灭活被证明有助于巨噬细胞杀死细胞内的白色念珠菌。使用C.白色念珠菌诱导的小鼠皮肤擦伤模型。总之，这些发现提供了一种新的过氧化氢酶光灭活方法来解决多重耐药念珠菌感染。大多数真菌微生物已经通过表达过氧化氢酶进化为过氧化氢。在此，发现来自大多数病原真菌（包括耳念珠菌）的过氧化氢酶可以被蓝光灭活，特别是在410 nm处。过氧化氢酶的光灭活使这些真菌细胞对H2O2产生剂和免疫细胞高度敏感。
Microbes have developed their own specific strategies to cope with reactive oxygen species (ROS). Catalase, a heme‐containing tetramer expressed in a broad range of aerobic fungi, shows remarkable efficiency in degrading hydrogen peroxide (H2O2) for fungal survival and host invasion. Here, it is demonstrated that catalase inactivation by blue light renders fungal cells highly susceptible to ROS attack. To confirm catalase as a major molecular target of blue light, wild type Candida albicans are systematically compared with a catalase‐deficient mutant strain regarding their susceptibility to ROS through 410 nm treatment. Upon testing a wide range of fungal species, it is found that intracellular catalase can be effectively and universally inactivated by 410 nm blue light. It is also found that photoinactivation of catalase in combination with ROS‐generating agents is highly effective in total eradication of various fungal species, including multiple Candida auris strains, the causative agent of the global fungal epidemic. In addition, photoinactivation of catalase is shown to facilitate macrophage killing of intracellular Candida albicans. The antifungal efficacy of catalase photoinactivation is further validated using a C. albicans‐induced mouse model of skin abrasion. Taken together, the findings offer a novel catalase‐photoinactivation approach to address multidrug‐resistant Candida infections. Most of the fungal microbes have evolved to scavenge H2O2 through expression of catalase. Here, it is found that catalase from most of pathogenic fungi (Candida auris included) can be inactivated by blue light, especially at 410 nm. Photoinactivation of catalase sensitizes these fungal cells highly susceptible to H2O2‐producing agents and immune cells.
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影响因子：
13.6
作者：
Dong PT;Zong C;Dagher Z;Hui J;Li J;Zhan Y;Zhang M;Mansour MK;Cheng JX
通讯作者：
Cheng JX
影响因子：
4.9
作者：
Dai, Tianhong;de Arce, Vida J. Bil;Hamblin, Michael R.
通讯作者：
Hamblin, Michael R.
影响因子：
11.8
作者：
Ascioglu, S;Rex, JH;Walsh, TJ
通讯作者：
Walsh, TJ
影响因子：
6.4
作者：
Arendrup, Maiken Cavling;Patterson, Thomas F.
通讯作者：
Patterson, Thomas F.
影响因子：
4.6
作者：
Johnson CJ;Kernien JF;Hoyer AR;Nett JE
通讯作者：
Nett JE