10.6084/M9.FIGSHARE.13182289
Si-Min Chen
Si-Min
Chen
Zui Zou
Zui
Zou
Shi-Yu Guo
Shi-Yu
Guo
Wei-Tong Hou
Wei-Tong
Hou
Xi-Ran Qiu
Xi-Ran
Qiu
Yu Zhang
Yu
Zhang
Li-Jun Song
Li-Jun
Song
Xin-Yu Hu
Xin-Yu
Hu
Yuan-Ying Jiang
Yuan-Ying
Jiang
Hui Shen
Hui
Shen
Mao-Mao An
Mao-Mao
An
Preventing <i>Candida albicans</i> from subverting host plasminogen for invasive infection treatment
<p><i>Candida albicans</i> is a common fungal pathogen in humans that colonizes the skin and mucosal surfaces of the majority healthy individuals. How <i>C. albicans</i> disseminates into the bloodstream and causes life-threatening systemic infections in immunocompromised patients remains unclear. Plasminogen system activation can degrade a variety of structural proteins <i>in vivo</i> and is involved in several homeostatic processes. Here, for the first time, we characterized that <i>C. albicans</i> could capture and “subvert” host plasminogen to invade host epithelial cell surface barriers through cell-wall localized Eno1 protein. We found that the “subverted” plasminogen system plays an important role in development of invasive infection caused by <i>C. albicans</i> in mice. Base on this finding, we discovered a mouse monoclonal antibody (mAb) 12D9 targeting <i>C. albicans</i> Eno1, with high affinity to the <sub>254</sub>FYKDGKYDL<sub>262</sub> motif in α-helices 6, β-sheet 6 (H6S6) loop and direct blocking activity for <i>C. albicans</i> capture host plasminogen. mAb 12D9 could prevent <i>C. albicans</i> from invading human epithelial and endothelial cells, and displayed antifungal activity and synergistic effect with anidulafungin or fluconazole in proof-of-concept <i>in vivo</i> studies, suggesting that blocking the function of cell surface Eno1 was effective for controlling invasive infection caused by <i>Candida</i> spp. In summary, our study provides the evidence of <i>C. albicans</i> invading host by “subverting” plasminogen system, suggesting a potential novel treatment strategy for invasive fungal infections.</p>
Medicine
Microbiology
Chemical Sciences not elsewhere classified
Ecology
Science Policy
Immunology
Cancer
Infectious Diseases
Virology
Taylor & Francis
2020
2020-11-03
2023-06-02
Dataset
1150958 Bytes
10.1080/22221751.2020.1840927
CC BY 4.0