Discovery of Novel Type II Bacteriocins Using a New High-Dimensional Bioinformatic Algorithm.
Front Immunol
; 11: 1873, 2020.
Article
em En
| MEDLINE
| ID: mdl-33013838
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 BACIIα algorithm-was created to identify and classify bacteriocin sequences with high fidelity. The BACIIα 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 BACIIα 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bacteriocinas
/
Biologia Computacional
/
Aprendizado de Máquina
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos