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Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans

Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provi...

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Autores principales: Dong, Shuai, Shi, Hongxi, Cao, Donghui, Wang, Yicun, Zhang, Xintong, Li, Yan, Gao, Xiang, Wang, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997605/
https://www.ncbi.nlm.nih.gov/pubmed/27558409
http://dx.doi.org/10.1038/srep32256
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author Dong, Shuai
Shi, Hongxi
Cao, Donghui
Wang, Yicun
Zhang, Xintong
Li, Yan
Gao, Xiang
Wang, Li
author_facet Dong, Shuai
Shi, Hongxi
Cao, Donghui
Wang, Yicun
Zhang, Xintong
Li, Yan
Gao, Xiang
Wang, Li
author_sort Dong, Shuai
collection PubMed
description Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.
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spelling pubmed-49976052016-09-01 Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans Dong, Shuai Shi, Hongxi Cao, Donghui Wang, Yicun Zhang, Xintong Li, Yan Gao, Xiang Wang, Li Sci Rep Article Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans. Nature Publishing Group 2016-08-25 /pmc/articles/PMC4997605/ /pubmed/27558409 http://dx.doi.org/10.1038/srep32256 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Dong, Shuai
Shi, Hongxi
Cao, Donghui
Wang, Yicun
Zhang, Xintong
Li, Yan
Gao, Xiang
Wang, Li
Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans
title Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans
title_full Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans
title_fullStr Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans
title_full_unstemmed Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans
title_short Novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by Candida albicans
title_sort novel nanoscale bacteriophage-based single-domain antibodies for the therapy of systemic infection caused by candida albicans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997605/
https://www.ncbi.nlm.nih.gov/pubmed/27558409
http://dx.doi.org/10.1038/srep32256
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