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Bibacillin 1: a two-component lantibiotic from Bacillus thuringiensis
Ryan Moreira1, Yi Yang1, Youran Luo1
1Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign Urbana IL 61822 USA vddonk@illinois.edu +1 217 244 5360.
RSC Chemical Biology
|September 13, 2024
Summary
Bibacillin 1, a novel two-component lantibiotic from Bacillus thuringiensis, exhibits potent bactericidal activity against Gram-positive bacteria, including ESKAPE pathogens. Its unique lipid II-independent mechanism and quorum sensing involvement distinguish it from other lantibiotics.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Lantibiotics are ribosomally synthesized and post-translationally modified peptides with antimicrobial properties.
- Two-component lantibiotics, like bibacillin 1, involve multiple peptides that act synergistically.
- Bacillus thuringiensis is a well-known entomopathogenic bacterium with a diverse range of secondary metabolites.
Purpose of the Study:
- To characterize bibacillin 1, a novel two-component lantibiotic from Bacillus thuringiensis.
- To elucidate the mechanism of action and cooperative activity of bibacillin 1.
- To investigate the potential role of bibacillin 1 in bacterial communication and its relationship with virulence factors.
Main Methods:
- Isolation and purification of bibacillin 1 components from Bacillus thuringiensis.
- Stereochemical analysis to determine the presence of modified amino acids (lanthionine and methyllanthionine).
- Bactericidal and hemolytic activity assays against various bacterial strains and erythrocytes.
- Mechanism of action studies, including lipid II-binding assays.
- Quorum sensing analysis through cross-reactivity assays.
Main Results:
- Bibacillin 1 consists of two peptides produced by the class II lanthipeptide synthetase Bib1M.
- Both peptides contain ll-methyllanthionine and dl-lanthionine, with non-overlapping ring patterns.
- Bibacillin 1 displayed cooperative bactericidal activity against Gram-positive bacteria, including ESKAPE pathogens, with weak hemolytic activity.
- Optimal activity was observed at a 1:1 ratio, but significant activity persisted at skewed ratios, suggesting complementary targets.
- The mechanism of action is lipid II-independent, differentiating it from haloduracin and lacticin 3147.
- One component showed cross-reactivity with the enterococcal cytolysin (CylLS'') regulatory system.
Conclusions:
- Bibacillin 1 is a novel two-component lantibiotic with potent antimicrobial activity against significant human pathogens.
- Its lipid II-independent killing mechanism and potential involvement in quorum sensing offer new insights into lantibiotic function.
- The findings raise questions about the ecological role of CylLS''-like natural products and their impact on lantibiotic expression.

