Lantibiotics are ribosomally synthesized peptides that contain multiple posttranslational modifications. Research on lantibiotics has increased recently, mainly due to their broad-spectrum antimicrobial activity, especially against some clinical Gram-positive pathogens. Many reports about various bacteriocins in the Bacillus cereus group have been published, but few were about lantibiotics. In this study, we identified 101 putative lanthipeptide gene clusters from 77 out of 223 strains of this group, and these gene clusters were further classified into 20 types according to their gene organization and the homologies of their functional genes. Among them, 18 types were novel and have not yet been experimentally verified. Two novel lantibiotics (thuricin 4A-4 and its derivative, thuricin 4A-4D) were identified in the type I-1 lanthipeptide gene cluster and showed activity against all tested Gram-positive bacteria. The mode of action of thuricin 4A-4 was studied, and we found that it acted as a bactericidal compound. The transcriptional analysis of four structural genes (thiA1, thiA2, thiA3, and thiA4) in the thuricin 4A gene cluster showed that only one structural gene, thiA4, showed efficient transcription in the exponential growth phase; the other three structural genes did not. In addition, the putative transmembrane protein ThiI was responsible for thuricin 4A-4 immunity. Genome analysis and functional verification illustrated that B. cereus group strains were a prolific source of novel lantibiotics. Bacteriocins are ribosomally synthesized peptides produced by bacteria and exhibit antimicrobial activity against other bacteria (either in the same species or across genera) (1); they include posttranslationally modified bacteriocins and unmodified bacteriocins (2). Lanthipeptides (lantibiotics) are peptides that undergo multiple posttranslational modifications, and these are the best-characterized modified bacteriocins (3). Modifications include the formation of meso-lanthionine and 3-methyllanthionine as well as dehydrated amino acids (Dha and Dhb). Lanthipeptides are classified into four different classes on the basis of their biosynthetic enzymes (4). In class I lanthipeptides, the dehydration is carried out by a dehydratase (LanB) and cyclization is catalyzed by a cyclase (LanC). Class II lanthipeptides are modified by LanM proteins, which perform both dehydration and cyclization. In class III and IV lanthipeptides, the dehydration and cyclization reactions are catalyzed by multifunctional enzymes (RamC/LabKC or LanL).The Bacillus cereus group currently contains eight species: B. anthracis, B. cereus, B. thuringiensis, B. cytotoxicus, B. weihenstephanensis, B. mycoides, B. pseudomycoides, and B. toyonensis (5, 6). To date, bacteriocins of the B. cereus group have been identified or characterized mainly in strains of B. cereus and B. thuringiensis. More than 20 bacteriocins have been reported in these two species (7,8). They are active against closely related bacilli, such as the foodborne pathogen B. cereus...
Lantibiotics are antimicrobial peptides with potential applications as the next generation of antimicrobials in the food industry and/or the pharmaceutical industry. Nisin has successfully been used as a food preservative for over 40 years, but its major drawback is its limited stability under neutral and alkaline pH conditions. To identify alternatives with better biochemical properties, we screened more than 100 strains of the Bacillus cereus group. Three novel lantibiotics, ticins A1 (4,062.98 Da), A3 (4,048.96 Da), and A4 (4,063.02 Da), which were highly thermostable (121°C for 30 min) and extremely pH tolerant (pH 2.0 to 9.0), were identified in Bacillus thuringiensis BMB3201. They all showed potent antimicrobial activities against all tested Gram-positive bacteria and greater activities than those of nisin A against Bacillus cereus and Listeria monocytogenes, two important foodborne pathogens. These three novel lantibiotics, with their extremely stable properties and potent antimicrobial activities, have the potential for use as biopreservatives. Bacteriocins are ribosomally synthesized antimicrobial peptides produced by various bacteria that are active against other bacteria either of the same species (narrow spectrum) or across genera (broad spectrum) (1). They are classified into two groups: posttranslationally modified bacteriocins and unmodified or cyclic bacteriocins (2). Lantibiotics (lanthipeptides) are the best-characterized modified bacteriocins, and their modifications include the formation of meso-lanthionine and 3-methyllanthionine residues, as well as dehydrated amino acids (Dha and Dhb) (3). Lanthionine (Lan) consists of two alanine residues cross-linked via a thioether linkage; 3-methyllanthionine (MeLan) contains one additional methyl group. Lanthipeptides are classified into four classes depending on their biosynthetic enzymes. For class I lanthipeptides, dehydration is carried out by a LanB dehydratase, and cyclization is catalyzed by a LanC cyclase. Class II lanthipeptides are modified by LanM lanthionine synthetases, which have an N-terminal dehydration domain and a C-terminal cyclization domain. For class III and IV lanthipeptides, the dehydration and cyclization reactions are catalyzed by multifunctional enzymes (RamC/LabKC or LanL).In the past decade, research on bacteriocins or lantibiotics has focused primarily on lactic acid bacteria (LAB), primarily because of their potential applications as preservatives in the food industry and/or as viable alternatives to antibiotics in medicine (2, 4). These bacteriocins also have several desirable properties that make them suitable for food preservation, as follows: (i) they are generally recognized as safe (GRAS), (ii) they are nontoxic to eukaryotic cells, (iii) they can be inactivated by digestive proteases, (iv) they are pH and heat tolerant, (v) they have a relatively broad antimicrobial spectrum against many Gram-positive foodborne pathogenic and spoilage bacteria, (vi) they show a bactericidal mode of action and no cross-resistance w...
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