Photoinactivation of Catalase Sensitizes Candida albicans and Candida auris to ROS-Producing Agents and Immune Cells

被引:20
|
作者
Dong, Pu-Ting [1 ,2 ]
Zhan, Yuewei [1 ,2 ]
Jusuf, Sebastian [1 ,2 ]
Hui, Jie [1 ,2 ]
Dagher, Zeina [3 ,4 ]
Mansour, Michael K. [3 ,4 ]
Cheng, Ji-Xin [1 ,2 ]
机构
[1] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA
[2] Boston Univ, Photon Ctr, Boston, MA 02215 USA
[3] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA
[4] Harvard Med Sch, Boston, MA 02115 USA
关键词
Candida auris; photoinactivation of catalase; reactive oxygen species; synergistic therapy; BLUE-LIGHT INACTIVATION; IN-VITRO; AMPHOTERICIN-B; EPIDEMIOLOGY; INFECTIONS; RESISTANCE; FLUCONAZOLE; INHIBITOR; BIOFILMS; YEASTS;
D O I
10.1002/advs.202104384
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
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页数:17
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