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Insight into the Antifungal Mechanism of Action of Human RNase N-terminus Derived Peptides
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 pa...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770517/ https://www.ncbi.nlm.nih.gov/pubmed/31540052 http://dx.doi.org/10.3390/ijms20184558 |
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author | Salazar, Vivian A. Arranz-Trullén, Javier Prats-Ejarque, Guillem Torrent, Marc Andreu, David Pulido, David Boix, Ester |
author_facet | Salazar, Vivian A. Arranz-Trullén, Javier Prats-Ejarque, Guillem Torrent, Marc Andreu, David Pulido, David Boix, Ester |
author_sort | Salazar, Vivian A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6770517 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67705172019-10-30 Insight into the Antifungal Mechanism of Action of Human RNase N-terminus Derived Peptides Salazar, Vivian A. Arranz-Trullén, Javier Prats-Ejarque, Guillem Torrent, Marc Andreu, David Pulido, David Boix, Ester Int J Mol Sci Article 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. MDPI 2019-09-14 /pmc/articles/PMC6770517/ /pubmed/31540052 http://dx.doi.org/10.3390/ijms20184558 Text en © 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/). |
spellingShingle | Article Salazar, Vivian A. Arranz-Trullén, Javier Prats-Ejarque, Guillem Torrent, Marc Andreu, David Pulido, David Boix, Ester Insight into the Antifungal Mechanism of Action of Human RNase N-terminus Derived Peptides |
title | Insight into the Antifungal Mechanism of Action of Human RNase N-terminus Derived Peptides |
title_full | Insight into the Antifungal Mechanism of Action of Human RNase N-terminus Derived Peptides |
title_fullStr | Insight into the Antifungal Mechanism of Action of Human RNase N-terminus Derived Peptides |
title_full_unstemmed | Insight into the Antifungal Mechanism of Action of Human RNase N-terminus Derived Peptides |
title_short | Insight into the Antifungal Mechanism of Action of Human RNase N-terminus Derived Peptides |
title_sort | insight into the antifungal mechanism of action of human rnase n-terminus derived peptides |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770517/ https://www.ncbi.nlm.nih.gov/pubmed/31540052 http://dx.doi.org/10.3390/ijms20184558 |
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