Dataset Information

Systematic Identification and Classification of ?-Lactamases Based on Sequence Similarity Criteria: ?-Lactamase Annotation.

ABSTRACT: ?-lactamases, the enzymes responsible for resistance to ?-lactam antibiotics, are widespread among prokaryotic genera. However, current ?-lactamase classification schemes do not represent their present diversity. Here, we propose a workflow to identify and classify ?-lactamases. Initially, a set of curated sequences was used as a model for the construction of profiles Hidden Markov Models (HMM), specific for each ?-lactamase class. An extensive, nonredundant set of ?-lactamase sequences was constructed from 7 different resistance proteins databases to test the methodology. The profiles HMM were improved for their specificity and sensitivity and then applied to fully assembled genomes. Five hierarchical classification levels are described, and a new class of ?-lactamases with fused domains is proposed. Our profiles HMM provide a better annotation of ?-lactamases, with classes and subclasses defined by objective criteria such as sequence similarity. This classification offers a solid base to the elaboration of studies on the diversity, dispersion, prevalence, and evolution of the different classes and subclasses of this critical enzymatic activity.

SUBMITTER: Silveira MC

PROVIDER: S-EPMC6131288 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Systematic Identification and Classification of β-Lactamases Based on Sequence Similarity Criteria: β-Lactamase Annotation.

Silveira Melise Chaves MC Azevedo da Silva Rangeline R Faria da Mota Fábio F Catanho Marcos M Jardim Rodrigo R R Guimarães Ana Carolina AC de Miranda Antonio B AB

Evolutionary bioinformatics online 20180910

β-lactamases, the enzymes responsible for resistance to β-lactam antibiotics, are widespread among prokaryotic genera. However, current β-lactamase classification schemes do not represent their present diversity. Here, we propose a workflow to identify and classify β-lactamases. Initially, a set of curated sequences was used as a model for the construction of profiles Hidden Markov Models (HMM), specific for each β-lactamase class. An extensive, nonredundant set of β-lactamase sequences was cons ...[more]

PMID: 30210232

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Project description:The human society faces a serious problem due to the widespread resistance to antibiotics in clinical practice. Most antibiotic biosynthesis gene clusters in actinobacteria contain genes for intrinsic self-resistance to the produced antibiotics, and it has been proposed that the antibiotic resistance genes in pathogenic bacteria originated in antibiotic-producing microorganisms. The model actinobacteria Streptomyces clavuligerus produces the β-lactam antibiotic cephamycin C, a class A β-lactamase, and the β lactamases inhibitor clavulanic acid, all of which are encoded in a gene supercluster; in addition, it synthesizes the β-lactamase inhibitory protein BLIP. The secreted clavulanic acid has a synergistic effect with the cephamycin produced by the same strain in the fight against competing microorganisms in its natural habitat. High levels of resistance to cephamycin/cephalosporin in actinobacteria are due to the presence (in their β-lactam clusters) of genes encoding PBPs which bind penicillins but not cephalosporins. We have revised the previously reported cephamycin C and clavulanic acid gene clusters and, in addition, we have searched for novel β-lactam gene clusters in protein databases. Notably, in S. clavuligerus and Nocardia lactamdurans, the β-lactamases are retained in the cell wall and do not affect the intracellular formation of isopenicillin N/penicillin N. The activity of the β-lactamase in S. clavuligerus may be modulated by the β-lactamase inhibitory protein BLIP at the cell-wall level. Analysis of the β-lactam cluster in actinobacteria suggests that these clusters have been moved by horizontal gene transfer between different actinobacteria and have culminated in S. clavuligerus with the organization of an elaborated set of genes designed for fine tuning of antibiotic resistance and cell wall remodeling for the survival of this Streptomyces species. This article is focused specifically on the enigmatic connection between β-lactam biosynthesis and β-lactam resistance mechanisms in the producer actinobacteria.

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Dataset Information

Systematic Identification and Classification of ?-Lactamases Based on Sequence Similarity Criteria: ?-Lactamase Annotation.

Publications

Systematic Identification and Classification of β-Lactamases Based on Sequence Similarity Criteria: β-Lactamase Annotation.

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