Exploring the mechanisms of action of human secretory RNase 3 and RNase 7 against Candida albicans
Salazar Montoya, Vivian Angélica (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Arranz Trullén, Javier (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Navarro, Susanna (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Blanco, José A (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Sánchez, Daniel (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Moussaoui, Mohammed (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Boix i Borràs, Esther (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Date:	2016
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad BFU2012-38965 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-795 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-728
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Cytotoxicity ; Host-pathogen interactions ; Infectious diseases ; Innate immunity
Published in:	MicrobiologyOpen, 2016 , ISSN 2045-8827

DOI: 10.1002/mbo3.373
PMID: 27277554

16 p, 722.5 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles