Preventing Candida albicans from subverting host plasminogen for invasive infection treatment
ABSTRACTCandida albicans is a common fungal pathogen in humans that colonizes the skin and mucosal surfaces of the majority healthy individuals. How C. albicans disseminates into the bloodstream and causes life-threatening systemic infections in immunocompromised patients remains unclear. Plasminoge...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2020-01-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2020.1840927 |
| _version_ | 1797265900748931072 |
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| author | Si-Min Chen Zui Zou Shi-Yu Guo Wei-Tong Hou Xi-Ran Qiu Yu Zhang Li-Jun Song Xin-Yu Hu Yuan-Ying Jiang Hui Shen Mao-Mao An |
| author_facet | Si-Min Chen Zui Zou Shi-Yu Guo Wei-Tong Hou Xi-Ran Qiu Yu Zhang Li-Jun Song Xin-Yu Hu Yuan-Ying Jiang Hui Shen Mao-Mao An |
| author_sort | Si-Min Chen |
| collection | DOAJ |
| description | ABSTRACTCandida albicans is a common fungal pathogen in humans that colonizes the skin and mucosal surfaces of the majority healthy individuals. How C. albicans 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 in vivo and is involved in several homeostatic processes. Here, for the first time, we characterized that C. albicans 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 C. albicans in mice. Base on this finding, we discovered a mouse monoclonal antibody (mAb) 12D9 targeting C. albicans Eno1, with high affinity to the 254FYKDGKYDL262 motif in α-helices 6, β-sheet 6 (H6S6) loop and direct blocking activity for C. albicans capture host plasminogen. mAb 12D9 could prevent C. albicans from invading human epithelial and endothelial cells, and displayed antifungal activity and synergistic effect with anidulafungin or fluconazole in proof-of-concept in vivo studies, suggesting that blocking the function of cell surface Eno1 was effective for controlling invasive infection caused by Candida spp. In summary, our study provides the evidence of C. albicans invading host by “subverting” plasminogen system, suggesting a potential novel treatment strategy for invasive fungal infections. |
| first_indexed | 2024-03-07T17:24:30Z |
| format | Article |
| id | doaj.art-cfcfe81d0baf426287c10c45a37cca8b |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-04-25T00:52:09Z |
| publishDate | 2020-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-cfcfe81d0baf426287c10c45a37cca8b2024-03-11T16:04:24ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512020-01-01912417243210.1080/22221751.2020.1840927Preventing Candida albicans from subverting host plasminogen for invasive infection treatmentSi-Min Chen0Zui Zou1Shi-Yu Guo2Wei-Tong Hou3Xi-Ran Qiu4Yu Zhang5Li-Jun Song6Xin-Yu Hu7Yuan-Ying Jiang8Hui Shen9Mao-Mao An10Department of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of ChinaDepartment of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of ChinaDepartment of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of ChinaDepartment of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Laboratory Diagnosis, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaDepartment of Pharmacology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaABSTRACTCandida albicans is a common fungal pathogen in humans that colonizes the skin and mucosal surfaces of the majority healthy individuals. How C. albicans 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 in vivo and is involved in several homeostatic processes. Here, for the first time, we characterized that C. albicans 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 C. albicans in mice. Base on this finding, we discovered a mouse monoclonal antibody (mAb) 12D9 targeting C. albicans Eno1, with high affinity to the 254FYKDGKYDL262 motif in α-helices 6, β-sheet 6 (H6S6) loop and direct blocking activity for C. albicans capture host plasminogen. mAb 12D9 could prevent C. albicans from invading human epithelial and endothelial cells, and displayed antifungal activity and synergistic effect with anidulafungin or fluconazole in proof-of-concept in vivo studies, suggesting that blocking the function of cell surface Eno1 was effective for controlling invasive infection caused by Candida spp. In summary, our study provides the evidence of C. albicans invading host by “subverting” plasminogen system, suggesting a potential novel treatment strategy for invasive fungal infections.https://www.tandfonline.com/doi/10.1080/22221751.2020.1840927C. albicansEnolasefungal infectionplasminogeninvasive candidiasis |
| spellingShingle | Si-Min Chen Zui Zou Shi-Yu Guo Wei-Tong Hou Xi-Ran Qiu Yu Zhang Li-Jun Song Xin-Yu Hu Yuan-Ying Jiang Hui Shen Mao-Mao An Preventing Candida albicans from subverting host plasminogen for invasive infection treatment Emerging Microbes and Infections C. albicans Enolase fungal infection plasminogen invasive candidiasis |
| title | Preventing Candida albicans from subverting host plasminogen for invasive infection treatment |
| title_full | Preventing Candida albicans from subverting host plasminogen for invasive infection treatment |
| title_fullStr | Preventing Candida albicans from subverting host plasminogen for invasive infection treatment |
| title_full_unstemmed | Preventing Candida albicans from subverting host plasminogen for invasive infection treatment |
| title_short | Preventing Candida albicans from subverting host plasminogen for invasive infection treatment |
| title_sort | preventing candida albicans from subverting host plasminogen for invasive infection treatment |
| topic | C. albicans Enolase fungal infection plasminogen invasive candidiasis |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2020.1840927 |
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