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Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties

Candida albicans is a deadly pathogen responsible for millions of mucosal and systemic infections per year. The pathobiology of C. albicans is largely dependent on the damaging and immunostimulatory properties of the peptide candidalysin (CL), a key virulence factor. When CL forms pores in the plasm...

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Autores principales: Russell, Charles M., Rybak, Jennifer A., Miao, Jian, Peters, Brian M., Barrera, Francisco N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9852700/
https://www.ncbi.nlm.nih.gov/pubmed/36581211
http://dx.doi.org/10.1016/j.jbc.2022.102829
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author Russell, Charles M.
Rybak, Jennifer A.
Miao, Jian
Peters, Brian M.
Barrera, Francisco N.
author_facet Russell, Charles M.
Rybak, Jennifer A.
Miao, Jian
Peters, Brian M.
Barrera, Francisco N.
author_sort Russell, Charles M.
collection PubMed
description Candida albicans is a deadly pathogen responsible for millions of mucosal and systemic infections per year. The pathobiology of C. albicans is largely dependent on the damaging and immunostimulatory properties of the peptide candidalysin (CL), a key virulence factor. When CL forms pores in the plasma membrane of epithelial cells, it activates a response network grounded in activation of the epidermal growth factor receptor. Prior reviews have characterized the resulting CL immune activation schemas but lacked insights into the molecular mechanism of CL membrane damage. We recently demonstrated that CL functions by undergoing a unique self-assembly process; CL forms polymers and loops in aqueous solution prior to inserting and forming pores in cell membranes. This mechanism, the first of its kind to be observed, informs new therapeutic avenues to treat Candida infections. Recently, variants of CL were identified in other Candida species, providing an opportunity to identify the residues that are key for CL to function. In this review, we connect the ability of CL to damage cell membranes to its immunostimulatory properties.
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spelling pubmed-98527002023-01-24 Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties Russell, Charles M. Rybak, Jennifer A. Miao, Jian Peters, Brian M. Barrera, Francisco N. J Biol Chem JBC Reviews Candida albicans is a deadly pathogen responsible for millions of mucosal and systemic infections per year. The pathobiology of C. albicans is largely dependent on the damaging and immunostimulatory properties of the peptide candidalysin (CL), a key virulence factor. When CL forms pores in the plasma membrane of epithelial cells, it activates a response network grounded in activation of the epidermal growth factor receptor. Prior reviews have characterized the resulting CL immune activation schemas but lacked insights into the molecular mechanism of CL membrane damage. We recently demonstrated that CL functions by undergoing a unique self-assembly process; CL forms polymers and loops in aqueous solution prior to inserting and forming pores in cell membranes. This mechanism, the first of its kind to be observed, informs new therapeutic avenues to treat Candida infections. Recently, variants of CL were identified in other Candida species, providing an opportunity to identify the residues that are key for CL to function. In this review, we connect the ability of CL to damage cell membranes to its immunostimulatory properties. American Society for Biochemistry and Molecular Biology 2022-12-26 /pmc/articles/PMC9852700/ /pubmed/36581211 http://dx.doi.org/10.1016/j.jbc.2022.102829 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle JBC Reviews
Russell, Charles M.
Rybak, Jennifer A.
Miao, Jian
Peters, Brian M.
Barrera, Francisco N.
Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties
title Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties
title_full Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties
title_fullStr Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties
title_full_unstemmed Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties
title_short Candidalysin: Connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties
title_sort candidalysin: connecting the pore forming mechanism of this virulence factor to its immunostimulatory properties
topic JBC Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9852700/
https://www.ncbi.nlm.nih.gov/pubmed/36581211
http://dx.doi.org/10.1016/j.jbc.2022.102829
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