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Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets

Antibiotic resistance (AR) is an acute problem that results in prolonged and debilitating illnesses. AR mortality worldwide is growing and causes a pressing need to research novel mechanisms of action and untested target molecules. This article presents in silico analyses of eight bacterial riboswit...

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Autores principales: Pavlova, Nikolet, Penchovsky, Robert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495176/
https://www.ncbi.nlm.nih.gov/pubmed/36139956
http://dx.doi.org/10.3390/antibiotics11091177
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author Pavlova, Nikolet
Penchovsky, Robert
author_facet Pavlova, Nikolet
Penchovsky, Robert
author_sort Pavlova, Nikolet
collection PubMed
description Antibiotic resistance (AR) is an acute problem that results in prolonged and debilitating illnesses. AR mortality worldwide is growing and causes a pressing need to research novel mechanisms of action and untested target molecules. This article presents in silico analyses of eight bacterial riboswitches for their suitability for antibacterial drug targets. Most bacterial riboswitches are located in the 5′-untranslated region of messenger RNAs, act as allosteric cis-acting gene control elements, and have not been found in humans before. Sensing metabolites, the riboswitches regulate the synthesis of vital cellular metabolites in various pathogenic bacteria. The analyses performed in this article represent a complete and informative genome-wide bioinformatics analysis of the adequacy of eight riboswitches as antibacterial drug targets in different pathogenic bacteria based on four criteria. Due to the ability of the riboswitch to control biosynthetic pathways and transport proteins of essential metabolites and the presence/absence of alternative biosynthetic pathways, we classified them into four groups based on their suitability for use as antibacterial drug targets guided by our in silico analyses. We concluded that some of them are promising targets for antibacterial drug discovery, such as the PreQ1, MoCo RNA, cyclic-di-GMP I, and cyclic-di-GMP II riboswitches.
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spelling pubmed-94951762022-09-23 Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets Pavlova, Nikolet Penchovsky, Robert Antibiotics (Basel) Article Antibiotic resistance (AR) is an acute problem that results in prolonged and debilitating illnesses. AR mortality worldwide is growing and causes a pressing need to research novel mechanisms of action and untested target molecules. This article presents in silico analyses of eight bacterial riboswitches for their suitability for antibacterial drug targets. Most bacterial riboswitches are located in the 5′-untranslated region of messenger RNAs, act as allosteric cis-acting gene control elements, and have not been found in humans before. Sensing metabolites, the riboswitches regulate the synthesis of vital cellular metabolites in various pathogenic bacteria. The analyses performed in this article represent a complete and informative genome-wide bioinformatics analysis of the adequacy of eight riboswitches as antibacterial drug targets in different pathogenic bacteria based on four criteria. Due to the ability of the riboswitch to control biosynthetic pathways and transport proteins of essential metabolites and the presence/absence of alternative biosynthetic pathways, we classified them into four groups based on their suitability for use as antibacterial drug targets guided by our in silico analyses. We concluded that some of them are promising targets for antibacterial drug discovery, such as the PreQ1, MoCo RNA, cyclic-di-GMP I, and cyclic-di-GMP II riboswitches. MDPI 2022-08-31 /pmc/articles/PMC9495176/ /pubmed/36139956 http://dx.doi.org/10.3390/antibiotics11091177 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pavlova, Nikolet
Penchovsky, Robert
Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets
title Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets
title_full Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets
title_fullStr Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets
title_full_unstemmed Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets
title_short Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets
title_sort bioinformatics and genomic analyses of the suitability of eight riboswitches for antibacterial drug targets
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495176/
https://www.ncbi.nlm.nih.gov/pubmed/36139956
http://dx.doi.org/10.3390/antibiotics11091177
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