title: Cerecidins, novel lantibiotics from Bacillus cereus with potent antimicrobial activity.
abstract: Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides that are widely produced by Gram-positive bacteria, including many species of the Bacillus group. In the present study, one novel gene cluster coding lantibiotic cerecidins was unveiled in Bacillus cereus strain As 1.1846 through genomic mining and PCR screening. The designated cer locus is different from that of conventional class II lantibiotics in that it included seven tandem precursor cerA genes, one modification gene (cerM), two processing genes (cerT and cerP), one orphan regulator gene (cerR), and two immunity genes (cerF and cerE). In addition, one unprecedented quorum sensing component, comQXPA, was inserted between cerM and cerR. The expression of cerecidins was not detected in this strain of B. cereus, which might be due to repressed transcription of cerM. We constitutively coexpressed cerA genes and cerM in Escherichia 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-resistant Staphylococcus aureus (MDRSA), vancomycin-resistant Enterococcus faecalis (VRE), and even Streptomyces.
authors: State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, People's Republic of China.
authors: Jian
authors: J
authors: Wang
authors: Li
authors: L
authors: Zhang
authors: Kunling
authors: K
authors: Teng
authors: Shutao
authors: S
authors: Sun
authors: Zhizeng
authors: Z
authors: Sun
authors: Jin
authors: J
authors: Zhong
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001409:Bacillus cereus / Q000737:chemistry*; D001430:Bacteriocins / Q000302:isolation & purification* / Q000494:pharmacology*; D053898:Biosynthetic Pathways; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D004269:DNA, Bacterial