Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus.
PLoS One
; 16(11): e0260003, 2021.
Article
in En
| MEDLINE
| ID: mdl-34780520
ABSTRACT
Mycobacterium abscessus (Mab) is one of the most drug resistant bacteria with a high treatment failure rate. Antimicrobial peptides (AMPs) are alternative therapeutic agents against this infection. This study was aimed to assess the in vitro activities of thirteen AMPs (S5, S52, S6, S61, S62, S63, KLK, KLK1, KLK2, Pug-1, Pug-2, Pug-3 and Pug-4) that have never been investigated against drug resistant Mab isolates. Only four novel modified AMPs (S61, S62, S63 and KLK1) provided the lowest minimum inhibitory concentration (MIC) values ranging from 200-400 µg/ml against the Mab ATCC19977 strain. These four potential AMPs were further tested with 16 clinical isolates of clarithromycin resistant Mab. The majority of the tested strains (10/16 isolates, 62.5%) showed ~99% kill by all four AMPs within 24 hours with an MIC <50 µg/ml. Only two isolates (12.5%) with acquired clarithromycin resistance, however, exhibited values <50 µg/ml of four potential AMPs, S61, S62, S63 and KLK1 after 3-days-incubation. At the MICs level, S63 showed the lowest toxicity with 1.50% hemolysis and 100% PBMC viability whereas KLK1 showed the highest hemolysis (10.21%) and lowest PBMC viability (93.52%). S61, S62 and S63 were further tested with clarithromycin-AMP interaction assays and found that 5/10 (50%) of selected isolates exhibited a synergistic interaction with 0.02-0.41 FICI values. This present study demonstrated the potential application of novel AMPs as an adjunctive treatment with clarithromycin against drug resistant Mab infection.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Resistance, Bacterial
/
Mycobacterium abscessus
/
Antimicrobial Peptides
/
Mycobacterium Infections, Nontuberculous
Limits:
Humans
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2021
Document type:
Article
Affiliation country:
Thailand