Discovery and Biosynthesis of Imidazolium Antibiotics from the Probiotic Bacillus licheniformis

Abstract

Antibiotic resistance is one of the world's most urgent public health problems, and novel antibiotics to kill drugresistant 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.

Characterization of Chemical Interactions between Clinical Drugs and the Oral Bacterium, Corynebacterium matruchotii, via Bioactivity-HiTES

“…Yellowish gum; UV (MeCN/H 2 O) λ max 220, 280 nm; 1 H (CD 3 OD, 700 MHz) δ 7.51 (1H, dt, J = 7.96, 1.00 Hz, H-7), 7.34 (1H, dt, J = 8.16, 0.95 Hz, H-4), 7.16 (1H, s, H-2), 7.10 (1H, ddd, J = 8.09, 6.93, 1.17 Antibacterial Activity Test of ACR (3), MIAA (4), IAA (5), and F-Ade (6). 41,42 The antibacterial activities of MIAA (4) and IAA (5) were examined against two Gram-negative bacterial strains (E. coli MG1655 and A. baumannii) and three Gram-positive bacterial strains (M. conceptionense, B. subtilis 168, and S. aureus USA300). Additionally, the antibacterial activities of ACR (3) and F-Ade (6) were evaluated against the same strains except for M. conceptionense.…”

Collagenase and Tyrosinase Inhibitory Compounds from Fish Gut Bacteria Ruegeria atlantica and Pseudoalteromonas neustonica

“…Moreover, our group recently confirmed that formaldehyde is produced from a bacterial species, Bacillus licheniformis. 40 To test this proposal, we performed biomimetic synthesis of 18 from 2-phenethylamine (17) and formaldehyde, two potential biosynthetic precursors of 18. We incubated 2-phenethylamine (17) and formaldehyde without bacteria in distilled water at 37 °C for 24 h (Figure 3).…”

An Engineered Microbial Consortium Provides Precursors for Fengycin Production by Bacillus subtilis

“…Lipopeptides are biosurfactants derived from natural resources, and these nontoxic biological compounds are important in the application of plant biological control . Fengycin, a well-known natural antibiotic, is a safe, nontoxic, and easily degradable antimicrobial lipopeptide produced by Bacillus and has significant inhibitory effects on the growth of filamentous fungi, thus providing a new candidate for the development of novel antifungal agents. − The first described and most common natural products from B. subtilis are cyclic lipopeptides . A nonribosomal peptide synthase (NRPS) gene cluster is responsible for the biosynthesis of fengycin .…”