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Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis

Ribosome-targeting antibiotics comprise over half of antibiotics used in medicine, but our fundamental knowledge of their binding sites is derived primarily from ribosome structures of non-pathogenic species. These include Thermus thermophilus, Deinococcus radiodurans and the archaean Haloarcula mar...

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Autores principales: Cooper, Helena B., Krause, Kurt L., Gardner, Paul P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039652/
https://www.ncbi.nlm.nih.gov/pubmed/36974140
http://dx.doi.org/10.7717/peerj.14969
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author Cooper, Helena B.
Krause, Kurt L.
Gardner, Paul P.
author_facet Cooper, Helena B.
Krause, Kurt L.
Gardner, Paul P.
author_sort Cooper, Helena B.
collection PubMed
description Ribosome-targeting antibiotics comprise over half of antibiotics used in medicine, but our fundamental knowledge of their binding sites is derived primarily from ribosome structures of non-pathogenic species. These include Thermus thermophilus, Deinococcus radiodurans and the archaean Haloarcula marismortui, as well as the commensal and sometimes pathogenic organism, Escherichia coli. Advancements in electron cryomicroscopy have allowed for the determination of more ribosome structures from pathogenic bacteria, with each study highlighting species-specific differences that had not been observed in the non-pathogenic structures. These observed differences suggest that more novel ribosome structures, particularly from pathogens, are required for a more accurate understanding of the level of diversity of the entire bacterial ribosome, with the potential of leading to innovative advancements in antibiotic research. In this study, high accuracy covariance and hidden Markov models were used to annotate ribosomal RNA and protein sequences respectively from genomic sequence, allowing us to determine the underlying ribosomal sequence diversity using phylogenetic methods. This analysis provided evidence that the current non-pathogenic ribosome structures are not sufficient representatives of some pathogenic bacteria, such as Campylobacter pylori, or of whole phyla such as Bacteroidota (Bacteroidetes).
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spelling pubmed-100396522023-03-26 Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis Cooper, Helena B. Krause, Kurt L. Gardner, Paul P. PeerJ Bioinformatics Ribosome-targeting antibiotics comprise over half of antibiotics used in medicine, but our fundamental knowledge of their binding sites is derived primarily from ribosome structures of non-pathogenic species. These include Thermus thermophilus, Deinococcus radiodurans and the archaean Haloarcula marismortui, as well as the commensal and sometimes pathogenic organism, Escherichia coli. Advancements in electron cryomicroscopy have allowed for the determination of more ribosome structures from pathogenic bacteria, with each study highlighting species-specific differences that had not been observed in the non-pathogenic structures. These observed differences suggest that more novel ribosome structures, particularly from pathogens, are required for a more accurate understanding of the level of diversity of the entire bacterial ribosome, with the potential of leading to innovative advancements in antibiotic research. In this study, high accuracy covariance and hidden Markov models were used to annotate ribosomal RNA and protein sequences respectively from genomic sequence, allowing us to determine the underlying ribosomal sequence diversity using phylogenetic methods. This analysis provided evidence that the current non-pathogenic ribosome structures are not sufficient representatives of some pathogenic bacteria, such as Campylobacter pylori, or of whole phyla such as Bacteroidota (Bacteroidetes). PeerJ Inc. 2023-03-22 /pmc/articles/PMC10039652/ /pubmed/36974140 http://dx.doi.org/10.7717/peerj.14969 Text en © 2023 Cooper et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Cooper, Helena B.
Krause, Kurt L.
Gardner, Paul P.
Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis
title Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis
title_full Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis
title_fullStr Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis
title_full_unstemmed Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis
title_short Finding priority bacterial ribosomes for future structural and antimicrobial research based upon global RNA and protein sequence analysis
title_sort finding priority bacterial ribosomes for future structural and antimicrobial research based upon global rna and protein sequence analysis
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039652/
https://www.ncbi.nlm.nih.gov/pubmed/36974140
http://dx.doi.org/10.7717/peerj.14969
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