Discovery and biosynthesis of imidazolium antibiotics from a probiotic Bacillus licheniformis

Abstract

AbstractAntibiotic resistance is one of the world’s most urgent public health problems and therefore novel antibiotics to kill drug-resistant bacteria are desperately needed. So far, natural product-derived small molecules have been the major sources for new antibiotics. Here we describe a family of antibacterial metabolites isolated from a probiotic bacterium Bacillus licheniformis. 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 E. coli MG1655 and Acinetobacter baumannii. We propose biosynthetic pathway of the characterized metabolites based on the precursor-feeding studies, chemical biological approach, biomimetic total synthesis, and biosynthetic genes knockout method.TOC/Abstract Graphic