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Membrane Activity of LL-37 Derived Antimicrobial Peptides against Enterococcus hirae: Superiority of SAAP-148 over OP-145

Authors :
Paulina Piller
Heimo Wolinski
Robert A. Cordfunke
Jan Wouter Drijfhout
Sandro Keller
Karl Lohner
Nermina Malanovic
Source :
Biomolecules, Vol 12, Iss 4, p 523 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

The development of antimicrobial agents against multidrug-resistant bacteria is an important medical challenge. Antimicrobial peptides (AMPs), human cathelicidin LL-37 and its derivative OP-145, possess a potent antimicrobial activity and were under consideration for clinical trials. In order to overcome some of the challenges to their therapeutic potential, a very promising AMP, SAAP-148 was designed. Here, we studied the mode of action of highly cationic SAAP-148 in comparison with OP-145 on membranes of Enterococcus hirae at both cellular and molecular levels using model membranes composed of major constituents of enterococcal membranes, that is, anionic phosphatidylglycerol (PG) and cardiolipin (CL). In all assays used, SAAP-148 was consistently more efficient than OP-145, but both peptides displayed pronounced time and concentration dependences in killing bacteria and performing at the membrane. At cellular level, Nile Red-staining of enterococcal membranes showed abnormalities and cell shrinkage, which is also reflected in depolarization and permeabilization of E. hirae membranes. At the molecular level, both peptides abolished the thermotropic phase transition and induced disruption of PG/CL. Interestingly, the membrane was disrupted before the peptides neutralized the negative surface charge of PG/CL. Our results demonstrate that SAAP-148, which kills bacteria at a significantly lower concentration than OP-145, shows stronger effects on membranes at the cellular and molecular levels.

Details

Language :
English
ISSN :
2218273X
Volume :
12
Issue :
4
Database :
Directory of Open Access Journals
Journal :
Biomolecules
Publication Type :
Academic Journal
Accession number :
edsdoj.46e80550e57d4f48b239ea04b59ff369
Document Type :
article
Full Text :
https://doi.org/10.3390/biom12040523