Ssa1-targeted antibody prevents host invasion by Candida albicans
IntroductionCandida albicans is a commensal fungus that colonizes most healthy individuals’ skin and mucosal surfaces but can also cause life-threatening invasive infections, particularly in immunocompromised patients. Despite antifungal treatment availability, drug resistance is increasing, and mor...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-07-01
|
| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1182914/full |
| _version_ | 1797772807991459840 |
|---|---|
| author | Xi-Ran Qiu Chen-Rui Shen Li-Wen Jiang Peng Ji Yu Zhang Wei-Tong Hou Wen Zhang Hui Shen Mao-Mao An |
| author_facet | Xi-Ran Qiu Chen-Rui Shen Li-Wen Jiang Peng Ji Yu Zhang Wei-Tong Hou Wen Zhang Hui Shen Mao-Mao An |
| author_sort | Xi-Ran Qiu |
| collection | DOAJ |
| description | IntroductionCandida albicans is a commensal fungus that colonizes most healthy individuals’ skin and mucosal surfaces but can also cause life-threatening invasive infections, particularly in immunocompromised patients. Despite antifungal treatment availability, drug resistance is increasing, and mortality rates remain unacceptably high. Heat shock protein Ssa1, a conserved member of the Hsp70 family in yeast, is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and enables C. albicans to cause maximal damage to host cells and induces disseminated and oropharyngeal disease.ResultHere we discovered a mouse monoclonal antibody (mAb 13F4) that targeting C. albicans Ssa1 with high affinity (EC50 = 39.78 ng/mL). mAb 13F4 prevented C. albicans from adhering to and invading human epithelial cells, displayed antifungal activity, and synergized with fluconazole in proof of concept in vivo studies. mAb 13F4 significantly prolonged the survival rate of the hematogenous disseminated candidiasis mice to 75%. We constructed a mAb 13F4 three-dimensional structure using homology modeling methods and found that the antigen-binding fragment (Fab) interacts with the Ssa1 N-terminus.DiscussionThese results suggest that blocking Ssa1 cell surface function may effectively control invasive C. albicans infections and provide a potential new treatment strategy for invasive fungal infections. |
| first_indexed | 2024-03-12T21:56:17Z |
| format | Article |
| id | doaj.art-a8bdb9bde2234aa2b6151acd5a0ddda6 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-03-12T21:56:17Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-a8bdb9bde2234aa2b6151acd5a0ddda62023-07-25T17:06:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-07-011410.3389/fmicb.2023.11829141182914Ssa1-targeted antibody prevents host invasion by Candida albicansXi-Ran Qiu0Chen-Rui Shen1Li-Wen Jiang2Peng Ji3Yu Zhang4Wei-Tong Hou5Wen Zhang6Hui Shen7Mao-Mao An8Department of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, ChinaIntroductionCandida albicans is a commensal fungus that colonizes most healthy individuals’ skin and mucosal surfaces but can also cause life-threatening invasive infections, particularly in immunocompromised patients. Despite antifungal treatment availability, drug resistance is increasing, and mortality rates remain unacceptably high. Heat shock protein Ssa1, a conserved member of the Hsp70 family in yeast, is a novel invasin that binds to host cell cadherins, induces host cell endocytosis, and enables C. albicans to cause maximal damage to host cells and induces disseminated and oropharyngeal disease.ResultHere we discovered a mouse monoclonal antibody (mAb 13F4) that targeting C. albicans Ssa1 with high affinity (EC50 = 39.78 ng/mL). mAb 13F4 prevented C. albicans from adhering to and invading human epithelial cells, displayed antifungal activity, and synergized with fluconazole in proof of concept in vivo studies. mAb 13F4 significantly prolonged the survival rate of the hematogenous disseminated candidiasis mice to 75%. We constructed a mAb 13F4 three-dimensional structure using homology modeling methods and found that the antigen-binding fragment (Fab) interacts with the Ssa1 N-terminus.DiscussionThese results suggest that blocking Ssa1 cell surface function may effectively control invasive C. albicans infections and provide a potential new treatment strategy for invasive fungal infections.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1182914/fullantibodySsa1Candida albicanssystemic infectionantifungal |
| spellingShingle | Xi-Ran Qiu Chen-Rui Shen Li-Wen Jiang Peng Ji Yu Zhang Wei-Tong Hou Wen Zhang Hui Shen Mao-Mao An Ssa1-targeted antibody prevents host invasion by Candida albicans Frontiers in Microbiology antibody Ssa1 Candida albicans systemic infection antifungal |
| title | Ssa1-targeted antibody prevents host invasion by Candida albicans |
| title_full | Ssa1-targeted antibody prevents host invasion by Candida albicans |
| title_fullStr | Ssa1-targeted antibody prevents host invasion by Candida albicans |
| title_full_unstemmed | Ssa1-targeted antibody prevents host invasion by Candida albicans |
| title_short | Ssa1-targeted antibody prevents host invasion by Candida albicans |
| title_sort | ssa1 targeted antibody prevents host invasion by candida albicans |
| topic | antibody Ssa1 Candida albicans systemic infection antifungal |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2023.1182914/full |
| work_keys_str_mv | AT xiranqiu ssa1targetedantibodypreventshostinvasionbycandidaalbicans AT chenruishen ssa1targetedantibodypreventshostinvasionbycandidaalbicans AT liwenjiang ssa1targetedantibodypreventshostinvasionbycandidaalbicans AT pengji ssa1targetedantibodypreventshostinvasionbycandidaalbicans AT yuzhang ssa1targetedantibodypreventshostinvasionbycandidaalbicans AT weitonghou ssa1targetedantibodypreventshostinvasionbycandidaalbicans AT wenzhang ssa1targetedantibodypreventshostinvasionbycandidaalbicans AT huishen ssa1targetedantibodypreventshostinvasionbycandidaalbicans AT maomaoan ssa1targetedantibodypreventshostinvasionbycandidaalbicans |