Marine-derived new peptaibols with antibacterial activities by targeting bacterial membrane phospholipids.
10.1016/j.apsb.2025.02.036
- Author:
Shang CHEN
1
;
Dong LIU
1
;
Liyang WANG
2
;
Aili FAN
1
;
Mengyue WU
1
;
Ning XU
3
;
Kui ZHU
2
;
Wenhan LIN
1
Author Information
1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
2. National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
3. The Technology Center for Protein Sciences, Tsinghua University, Beijing 100084, China.
- Publication Type:Journal Article
- Keywords:
Antibiotic;
Bactericidal activity;
Marine fungus;
NRPS;
Natural product;
Peptaibol;
Phosphatidylglycerol;
Phospholipid
- From:
Acta Pharmaceutica Sinica B
2025;15(5):2764-2777
- CountryChina
- Language:English
-
Abstract:
Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.
