Dataset Information

Discovery of Novel Type II Bacteriocins Using a New High-Dimensional Bioinformatic Algorithm.

ABSTRACT: Antimicrobial compounds first arose in prokaryotes by necessity for competitive self-defense. In this light, prokaryotes invented the first host defense peptides. Among the most well-characterized of these peptides are class II bacteriocins, ribosomally-synthesized polypeptides produced chiefly by Gram-positive bacteria. In the current study, a tensor search protocol-the BACII? algorithm-was created to identify and classify bacteriocin sequences with high fidelity. The BACII? algorithm integrates a consensus signature sequence, physicochemical and genomic pattern elements within a high-dimensional query tool to select for bacteriocin-like peptides. It accurately retrieved and distinguished virtually all families of known class II bacteriocins, with an 86% specificity. Further, the algorithm retrieved a large set of unforeseen, putative bacteriocin peptide sequences. A recently-developed machine-learning classifier predicted the vast majority of retrieved sequences to induce negative Gaussian curvature in target membranes, a hallmark of antimicrobial activity. Prototypic bacteriocin candidate sequences were synthesized and demonstrated potent antimicrobial efficacy in vitro against a broad spectrum of human pathogens. Therefore, the BACII? algorithm expands the scope of prokaryotic host defense bacteriocins and enables an innovative bioinformatics discovery strategy. Understanding how prokaryotes have protected themselves against microbial threats over eons of time holds promise to discover novel anti-infective strategies to meet the challenge of modern antibiotic resistance.

SUBMITTER: Yount NY

PROVIDER: S-EPMC7494827 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Discovery of Novel Type II Bacteriocins Using a New High-Dimensional Bioinformatic Algorithm.

Yount Nannette Y NY Weaver David C DC de Anda Jaime J Lee Ernest Y EY Lee Michelle W MW Wong Gerard C L GCL Yeaman Michael R MR

Frontiers in immunology 20200903

Antimicrobial compounds first arose in prokaryotes by necessity for competitive self-defense. In this light, prokaryotes invented the first host defense peptides. Among the most well-characterized of these peptides are class II bacteriocins, ribosomally-synthesized polypeptides produced chiefly by Gram-positive bacteria. In the current study, a tensor search protocol-the BACIIα algorithm-was created to identify and classify bacteriocin sequences with high fidelity. The BACIIα algorithm integrate ...[more]

PMID: 33013838

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Project description:BACKGROUND:Circular bacteriocins are antimicrobial peptides produced by bacteria with a N and C termini ligation. They have desirable properties such as activity at low concentrations along with thermal, pH and proteolytic resistance. There are twenty experimentally confirmed circular bacteriocins as part of bacteriocin gene clusters, with transport, membrane and immunity proteins. Traditionally, novel antimicrobials are found by testing large numbers of isolates against indicator strains, with no promise of corresponding novel sequence. RESULTS:Through bioprospecting publicly available sequence databases, we identified ninety-nine circular bacteriocins across a variety of bacteria bringing the total to 119. They were grouped into two families within class I modified bacteriocins (i and ii) and further divided into subfamilies based on similarity to experimentally confirmed circular bacteriocins. Within subfamilies, sequences overwhelmingly shared similar characteristics such as sequence length, presence of a polybasic region, conserved locations of aromatic residues, C and N termini, gene clusters similarity, translational coupling and hydrophobicity profiles. At least ninety were predicted to be putatively functional based on gene clusters. Furthermore, bacteriocins identified from Enterococcus, Staphylococcus and Streptococcus species may have activity against clinically relevant strains, due to the presence of putative immunity genes required for expression in a toxin-antitoxin system. Some strains such as Paenibacillus larvae subsp. pulvifaciens SAG 10367 contained multiple circular bacteriocin gene clusters from different subfamilies, while some strains such as Bacillus cereus BCE-01 contained clusters with multiple circular bacteriocin structural genes. CONCLUSIONS:Sequence analysis provided rapid insight into identification of novel, putative circular bacteriocins, as well as conserved genes likely essential for circularisation. This represents an expanded library of putative antimicrobial proteins which are potentially active against human, plant and animal pathogens.

Dataset Information

Discovery of Novel Type II Bacteriocins Using a New High-Dimensional Bioinformatic Algorithm.

Publications

Discovery of Novel Type II Bacteriocins Using a New High-Dimensional Bioinformatic Algorithm.

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