TY - JOUR
T1 - Insight into the antifungal mechanism of action of human RNase N-terminus derived peptides
AU - Salazar, Vivian A.
AU - Arranz-Trullén, Javier
AU - Prats-Ejarque, Guillem
AU - Torrent, Marc
AU - Andreu, David
AU - Pulido, David
AU - Boix, Ester
PY - 2019/9/2
Y1 - 2019/9/2
N2 - © 2019 by the authors. Candida albicans is a polymorphic fungus responsible formucosal 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 RNaseswas sufficient to reproducemost 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 biofilmeradication 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.
AB - © 2019 by the authors. Candida albicans is a polymorphic fungus responsible formucosal 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 RNaseswas sufficient to reproducemost 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 biofilmeradication 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.
KW - Antifungal activity
KW - Antimicrobial peptides
KW - Biofilms
KW - Candida albicans
KW - RNaseA superfamily
UR - https://ddd.uab.cat/record/213242
U2 - https://doi.org/10.3390/ijms20184558
DO - https://doi.org/10.3390/ijms20184558
M3 - Article
C2 - 31540052
VL - 20
M1 - 4558
ER -