Discovery and Biosynthesis of Imidazolium Antibiotics from the Probiotic Bacillus licheniformis.
J Nat Prod
; 86(4): 850-859, 2023 04 28.
Article
in En
| MEDLINE
| ID: mdl-36921254
ABSTRACT
Antibiotic resistance is one of the world's most urgent public health problems, and novel antibiotics to kill drug-resistant bacteria are needed. Natural product-derived small molecules have been the major source of new antibiotics. Here we describe a family of antibacterial metabolites isolated from a probiotic bacterium, Bacillus licheniformis. A cross-streaking assay followed by activity-guided isolation yielded a novel antibacterial metabolite, bacillimidazole G, which possesses a rare imidazolium ring in the structure, showing MIC values of 0.7-2.6 µg/mL against human pathogenic Gram-positive and Gram-negative bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and a lipopolysaccharide (LPS)-lacking Acinetobacter baumannii ΔlpxC. Bacillimidazole G also lowered MICs of colistin, a Gram-negative antibiotic, up to 8-fold against wild-type Escherichia coli MG1655 and A. baumannii. We propose a biosynthetic pathway to the characterized metabolites based on precursor-feeding studies, a chemical biological approach, biomimetic total synthesis, and a biosynthetic gene knockout method.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Methicillin-Resistant Staphylococcus aureus
/
Bacillus licheniformis
Limits:
Humans
Language:
En
Journal:
J Nat Prod
Year:
2023
Document type:
Article