BAGEL3: automated identification of genes encoding bacteriocins and (non-)bactericidal posttranslationally modified peptides

Heel, Auke J. van; Jong, Anne de; Montalbán-López, Manuel; Kok, Jan; Kuipers, Oscar P.

doi:10.1093/nar/gkt391

Cited by 419 publications

(369 citation statements)

References 23 publications

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“…With increasing understanding of lantibiotic biosynthesis apparatus and accumulation of sequenced genomes, the age of genomic mining is coming (38). In recent years, a great number of gene clusters of known or unknown lantibiotics have been revealed by genomic mining in broad spectra of species, even including extensively studied actinomycetes, and many of them are then discovered to produce lantibiotics (39,40).…”

Section: Discussionmentioning

confidence: 99%

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Wang

Zhang

Teng

et al. 2014

Appl Environ Microbiol

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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.

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Section: Discussionmentioning

confidence: 99%

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Wang

Zhang

Teng

et al. 2014

Appl Environ Microbiol

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“…The web-based tool BAGEL (version 2) was used to predict putative bacteriocins in the L. crispatus strains (van Heel et al, 2013). BAGEL uses a combination of ORF prediction tools, databases of known bacteriocins and motif databases to identify potential bacteriocin genes.…”

Section: Methodsmentioning

confidence: 99%

“…(van Heel et al, 2013) was used to identify bacteriolysin genes. The genes were given random identifiers 1-4 for inter-strain comparison.…”

Section: D-/l-lactic Acidmentioning

confidence: 99%

Comparison of Lactobacillus crispatus isolates from Lactobacillus-dominated vaginal microbiomes with isolates from microbiomes containing bacterial vaginosis-associated bacteria

et al. 2016

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Vaginal lactobacilli can inhibit colonization by and growth of other bacteria, thereby preventing development of bacterial vaginosis (BV). Amongst the lactobacilli, Lactobacillus crispatus appears to be particularly effective at inhibiting growth of BV-associated bacteria. Nonetheless, some women who are colonized with this species can still develop clinical BV. Therefore, we sought to determine whether strains of L. crispatus that colonize women with lactobacillidominated vaginal microbiomes are distinct from strains that colonize women who develop BV. The genomes of L. crispatus isolates from four women with lactobacilli-dominated vaginal microbiomes (,1 % 16S rRNA reads above threshold from genera other than Lactobacillus) and four women with microbiomes containing BV-associated bacteria (.12 % 16S rRNA reads from bacterial taxa associated with BV) were sequenced and compared. Lactic acid production by the different strains was quantified. Phage induction in the strains was also analysed. There was considerable genetic diversity between strains, and several genes were exclusive to either the strains from Lactobacillus-dominated microbiomes or those containing BV-associated bacteria. Overall, strains from microbiomes dominated by lactobacilli did not differ from strains from microbiomes containing BV-associated bacteria with respect to lactic acid production. All of the strains contained multiple phage, but there was no clear distinction between the presence or absence of BV-associated bacteria with respect to phage-induced lysis. Genes found to be exclusive to the Lactobacillus-dominated versus BV-associated bacteria-containing microbiomes could play a role in the maintenance of vaginal health and the development of BV, respectively.

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“…Genomes in the fasta format were individually uploaded to BAGEL3 (24) and antiSMASH (25) software to identify putative proteins related to bacteriocin production. Result files containing the amino acid sequences of the identified proteins were copied as text (.txt) files for sequence comparisons.…”

Section: Data Setsmentioning

confidence: 99%

Distribution and Genetic Diversity of Bacteriocin Gene Clusters in Rumen Microbial Genomes

Azevedo

Bento

Ruiz

et al. 2015

Appl Environ Microbiol

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b Some species of ruminal bacteria are known to produce antimicrobial peptides, but the screening procedures have mostly been based on in vitro assays using standardized methods. Recent sequencing efforts have made available the genome sequences of hundreds of ruminal microorganisms. In this work, we performed genome mining of the complete and partial genome sequences of 224 ruminal bacteria and 5 ruminal archaea to determine the distribution and diversity of bacteriocin gene clusters. A total of 46 bacteriocin gene clusters were identified in 33 strains of ruminal bacteria. Twenty gene clusters were related to lanthipeptide biosynthesis, while 11 gene clusters were associated with sactipeptide production, 7 gene clusters were associated with class II bacteriocin production, and 8 gene clusters were associated with class III bacteriocin production. The frequency of strains whose genomes encode putative antimicrobial peptide precursors was 14.4%. Clusters related to the production of sactipeptides were identified for the first time among ruminal bacteria. BLAST analysis indicated that the majority of the gene clusters (88%) encoding putative lanthipeptides contained all the essential genes required for lanthipeptide biosynthesis. Most strains of Streptococcus (66.6%) harbored complete lanthipeptide gene clusters, in addition to an open reading frame encoding a putative class II bacteriocin. Albusin B-like proteins were found in 100% of the Ruminococcus albus strains screened in this study. The in silico analysis provided evidence of novel biosynthetic gene clusters in bacterial species not previously related to bacteriocin production, suggesting that the rumen microbiota represents an underexplored source of antimicrobial peptides.T he production of low-molecular-weight antimicrobial peptides is a trait widely distributed among species of bacteria and archaea (1). Although a variety of functions has been assigned to these compounds (e.g., toxins, virulence factors, bacterial hormones), the bacteriocins have mainly been investigated due to their potential as alternatives to antibiotics and food preservatives (2-4). With the rise in antibiotic resistance among commensal and pathogenic strains of bacteria, there is an urgent need to identify and develop novel therapeutic strategies for clinical applications in human and animal health (5).Bacteriocins are often defined as ribosomally synthesized antimicrobial peptides produced by bacteria or archaea (6). Bacteriocins show great diversity in their chemical structures and mechanisms of action, and at least four main groups have been proposed to classify these antimicrobial agents (7). Class I contains posttranslationally modified antimicrobial peptides, such as lanthipeptides, sactipeptides, and lasso peptides, which differ in their molecular structures, their mechanisms of action, and the enzymatic apparatuses involved in modifying the precursor peptides (7,8). Class II bacteriocins consist of antimicrobial peptides without posttranslationally modified residues and ca...

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BAGEL3: automated identification of genes encoding bacteriocins and (non-)bactericidal posttranslationally modified peptides

Cited by 419 publications

References 23 publications

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Cerecidins, Novel Lantibiotics from Bacillus cereus with Potent Antimicrobial Activity

Comparison of Lactobacillus crispatus isolates from Lactobacillus-dominated vaginal microbiomes with isolates from microbiomes containing bacterial vaginosis-associated bacteria

Distribution and Genetic Diversity of Bacteriocin Gene Clusters in Rumen Microbial Genomes

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