Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans

Human antimicrobial RNases, which belong to the vertebrate RNase A superfamily and are secreted upon infection, display a wide spectrum of antipathogen activities. In this work, we examined the antifungal activity of the eosinophil RNase 3 and the skin‐derived RNase 7, two proteins expressed by inna...

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Main Authors:	Salazar, Vivian A., Arranz‐Trullén, Javier, Navarro, Susanna, Blanco, Jose A., Sánchez, Daniel, Moussaoui, Mohammed, Boix, Ester
Format:	Online
Language:	English
Published:	John Wiley and Sons Inc. 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061719/

id	pubmed-5061719
recordtype	oai_dc
spelling	pubmed-50617192016-10-24 Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans Salazar, Vivian A. Arranz‐Trullén, Javier Navarro, Susanna Blanco, Jose A. Sánchez, Daniel Moussaoui, Mohammed Boix, Ester Original Research Human antimicrobial RNases, which belong to the vertebrate RNase A superfamily and are secreted upon infection, display a wide spectrum of antipathogen activities. In this work, we examined the antifungal activity of the eosinophil RNase 3 and the skin‐derived RNase 7, two proteins expressed by innate cell types that are directly involved in the host defense against fungal infection. Candida albicans has been selected as a suitable working model for testing RNase activities toward a eukaryotic pathogen. We explored the distinct levels of action of both RNases on yeast by combining cell viability and membrane model assays together with protein labeling and confocal microscopy. Site‐directed mutagenesis was applied to ablate either the protein active site or the key anchoring region for cell binding. This is the first integrated study that highlights the RNases’ dual mechanism of action. Along with an overall membrane‐destabilization process, the RNases could internalize and target cellular RNA. The data support the contribution of the enzymatic activity for the antipathogen action of both antimicrobial proteins, which can be envisaged as suitable templates for the development of novel antifungal drugs. We suggest that both human RNases work as multitasking antimicrobial proteins that provide a first line immune barrier. John Wiley and Sons Inc. 2016-06-08 /pmc/articles/PMC5061719/ /pubmed/27277554 http://dx.doi.org/10.1002/mbo3.373 Text en © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Salazar, Vivian A. Arranz‐Trullén, Javier Navarro, Susanna Blanco, Jose A. Sánchez, Daniel Moussaoui, Mohammed Boix, Ester
spellingShingle	Salazar, Vivian A. Arranz‐Trullén, Javier Navarro, Susanna Blanco, Jose A. Sánchez, Daniel Moussaoui, Mohammed Boix, Ester Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans
author_facet	Salazar, Vivian A. Arranz‐Trullén, Javier Navarro, Susanna Blanco, Jose A. Sánchez, Daniel Moussaoui, Mohammed Boix, Ester
author_sort	Salazar, Vivian A.
title	Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans
title_short	Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans
title_full	Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans
title_fullStr	Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans
title_full_unstemmed	Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans
title_sort	exploring the mechanisms of action of human secretory rnase 3 and rnase 7 against candida albicans
description	Human antimicrobial RNases, which belong to the vertebrate RNase A superfamily and are secreted upon infection, display a wide spectrum of antipathogen activities. In this work, we examined the antifungal activity of the eosinophil RNase 3 and the skin‐derived RNase 7, two proteins expressed by innate cell types that are directly involved in the host defense against fungal infection. Candida albicans has been selected as a suitable working model for testing RNase activities toward a eukaryotic pathogen. We explored the distinct levels of action of both RNases on yeast by combining cell viability and membrane model assays together with protein labeling and confocal microscopy. Site‐directed mutagenesis was applied to ablate either the protein active site or the key anchoring region for cell binding. This is the first integrated study that highlights the RNases’ dual mechanism of action. Along with an overall membrane‐destabilization process, the RNases could internalize and target cellular RNA. The data support the contribution of the enzymatic activity for the antipathogen action of both antimicrobial proteins, which can be envisaged as suitable templates for the development of novel antifungal drugs. We suggest that both human RNases work as multitasking antimicrobial proteins that provide a first line immune barrier.
publisher	John Wiley and Sons Inc.
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061719/
_version_	1613681800255635456

Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans

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