Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are widely produced by Gram-positive bacteria, including many species of theBacillus group. In the present study, one novel gene cluster coding lantibiotic cerecidins was unveiled inBacillus cereus strain As 1.1846 through genomic mining and PCR screening. The designatedcer locus is different from that of conventional class II lantibiotics in that it included seven tandem precursorcerA genes, one modification gene (cerM ), two processing genes (cerT andcerP ), one orphan regulator gene (cerR ), and two immunity genes (cerF andcerE ). In addition, one unprecedented quorum sensing component,comQXPA , was inserted betweencerM andcerR . The expression of cerecidins was not detected in this strain ofB. cereus , which might be due to repressed transcription ofcerM . We constitutively coexpressedcerA genes andcerM inEscherichia coli , and purified precerecidins were proteolytically processed with the endoproteinase GluC and a truncated version of putative serine protease CerP. Thus, two natural variants of cerecidins A1 and A7 were obtained which contained two terminal nonoverlapping thioether rings rarely found in lantibiotics. Both cerecidins A1 and A7 were active against a broad spectrum of Gram-positive bacteria. Cerecidin A7, especially its mutant Dhb13A, showed remarkable efficacy against multidrug-resistantStaphylococcus aureus (MDRSA), vancomycin-resistantEnterococcus faecalis (VRE), and evenStreptomyces .