Insight into the antifungal mechanism of action of human RNase N-terminus derived peptides
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- dc.contributor.author Salazar, Vivian A.
- dc.contributor.author Arranz-Trullén, Javier
- dc.contributor.author Prats-Ejarque, Guillem
- dc.contributor.author Torrent, Marc
- dc.contributor.author Andreu Martínez, David
- dc.contributor.author Pulido, David
- dc.contributor.author Boix, Ester
- dc.date.accessioned 2019-10-09T07:51:35Z
- dc.date.available 2019-10-09T07:51:35Z
- dc.date.issued 2019
- dc.description.abstract Candida albicans is a polymorphic fungus responsible for mucosal and skin infections. Candida cells establish themselves into biofilm communities resistant to most currently available antifungal agents. An increase of severe infections ensuing in fungal septic shock in elderly or immunosuppressed patients, along with the emergence of drug-resistant strains, urge the need for the development of alternative antifungal agents. In the search for novel antifungal drugs our laboratory demonstrated that two human ribonucleases from the vertebrate-specific RNaseA superfamily, hRNase3 and hRNase7, display a high anticandidal activity. In a previous work, we proved that the N-terminal region of the RNases was sufficient to reproduce most of the parental protein bactericidal activity. Next, we explored their potency against a fungal pathogen. Here, we have tested the N-terminal derived peptides that correspond to the eight human canonical RNases (RN1-8) against planktonic cells and biofilms of C. albicans. RN3 and RN7 peptides displayed the most potent inhibitory effect with a mechanism of action characterized by cell-wall binding, membrane permeabilization and biofilm eradication activities. Both peptides are able to eradicate planktonic and sessile cells, and to alter their gene expression, reinforcing its role as a lead candidate to develop novel antifungal and antibiofilm therapies.
- dc.description.sponsorship This research was funded by the Ministerio de Economía y Competitividad (SAF2017-82158-R and SAF2015-66007P, Fundació La Marató de TV3 (20180310) and Generalitat de Catalunya (2016-PROD-00060). M.T. would like to acknowledge support from the Programa Ramon y Cajal (RYC-2012-09999) and the European Society of Clinical Microbiology and Infectious Diseases though ans ESCMID-2016 grant.
- dc.format.mimetype application/pdf
- dc.identifier.citation Salazar VA, Arranz-Trullén J, Prats-Ejarque G, Torrent M, Andreu D, Pulido D et al. Insight into the antifungal mechanism of action of human RNase N-terminus derived peptides. Int J Mol Sci. 2019; 20(18):4558. DOI: 10.3390/ijms20184558
- dc.identifier.doi http://dx.doi.org/10.3390/ijms20184558
- dc.identifier.issn 1422-0067
- dc.identifier.uri http://hdl.handle.net/10230/42413
- dc.language.iso eng
- dc.publisher MDPI
- dc.relation.ispartof International Journal of Molecular Sciences. 2019; 20(18):4558
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-82158-R
- dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-66007-P
- dc.rights © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Antimicrobial peptides
- dc.subject.keyword Candida albicans
- dc.subject.keyword Biofilms
- dc.subject.keyword Antifungal activity
- dc.subject.keyword RNaseA superfamily
- dc.title Insight into the antifungal mechanism of action of human RNase N-terminus derived peptides
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion