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Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci

BACKGROUND AND AIM: Global Health is threatened by the rapid emergence of multidrug-resistant bacteria. Antibiotic resistomes rapidly evolve, yet conserved motifs elucidated in our study have the potential for future drug targets for precision medicine. This study aimed to identify conserved genetic...

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Autores principales: Memili, Aylin, Kutchy, Naseer, Braimah, Olubumi A., Morenikeji, Olanrewaju B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Veterinary World 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682389/
https://www.ncbi.nlm.nih.gov/pubmed/36425127
http://dx.doi.org/10.14202/vetworld.2022.2407-2413
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author Memili, Aylin
Kutchy, Naseer
Braimah, Olubumi A.
Morenikeji, Olanrewaju B.
author_facet Memili, Aylin
Kutchy, Naseer
Braimah, Olubumi A.
Morenikeji, Olanrewaju B.
author_sort Memili, Aylin
collection PubMed
description BACKGROUND AND AIM: Global Health is threatened by the rapid emergence of multidrug-resistant bacteria. Antibiotic resistomes rapidly evolve, yet conserved motifs elucidated in our study have the potential for future drug targets for precision medicine. This study aimed to identify conserved genetic sequences and their evolutionary pathways among vancomycin-resistant Enterococcus species such as Enterococcus faecium and Enterococcus faecalis. MATERIALS AND METHODS: We retrieved a total of 26 complete amino acid and nucleotide sequences of resistance determinant genes against vancomycin (vanA and vanB), streptomycin (aac-aah), and penicillin (pbp5) from the publicly available genetic sequence database, GenBank. The sequences were comprised of bacteria classified under the genera of Enterococcus, Staphylococcus, Amycolatopsis, Ruminococcus, and Clostridium. Sequences were aligned with Clustal Omega Multiple Sequence Alignment program and Percent Identity Matrices were derived. Phylogenetic analyses to elucidate evolutionary relationships between sequences were conducted with the neighbor-end joining method through the Molecular Evolutionary Genetics Analysis (MEGAX) software, developed by the Institute of Molecular Evolutionary Genetics at Pennsylvania State University. Subsequent network analyses of the resistance gene, vanB, within E. faecium were derived from ScanProsite and InterPro. RESULTS: We observed the highest nucleotide sequence similarity of vanA regions within strains of E. faecium (100%) and E. faecalis (100%). Between Enterococcus genera, we continued to observe high sequence conservation for vanA and vanB, up to 99.9% similarity. Phylogenetic tree analyses suggest rapid acquisition of these determinants between strains within vanA and vanB, particularly between strains of Enterococcus genera, which may be indicative of horizontal gene transfer. Within E. faecium, Adenosine 5’-Triphosphate (ATP)-Grasp and D-ala-D-ala ligase (Ddl) were found as conserved domains of vanA and vanB. We additionally found that there is notable sequence conservation, up to 66.67%, between resistomes against vancomycin and streptomycin among E. faecium. CONCLUSION: Resistance genes against vancomycin have highly conserved sequences between strains of Enterococcus bacteria. These conserved sequences within vanA and vanB encode for ATP-Grasp and Ddl motifs, which have functional properties for maintaining cell wall integrity. High sequence conservation is also observed among resistance genes against penicillin and streptomycin, which can inform future drug targets for broader spectrum therapies.
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spelling pubmed-96823892022-11-23 Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci Memili, Aylin Kutchy, Naseer Braimah, Olubumi A. Morenikeji, Olanrewaju B. Vet World Research Article BACKGROUND AND AIM: Global Health is threatened by the rapid emergence of multidrug-resistant bacteria. Antibiotic resistomes rapidly evolve, yet conserved motifs elucidated in our study have the potential for future drug targets for precision medicine. This study aimed to identify conserved genetic sequences and their evolutionary pathways among vancomycin-resistant Enterococcus species such as Enterococcus faecium and Enterococcus faecalis. MATERIALS AND METHODS: We retrieved a total of 26 complete amino acid and nucleotide sequences of resistance determinant genes against vancomycin (vanA and vanB), streptomycin (aac-aah), and penicillin (pbp5) from the publicly available genetic sequence database, GenBank. The sequences were comprised of bacteria classified under the genera of Enterococcus, Staphylococcus, Amycolatopsis, Ruminococcus, and Clostridium. Sequences were aligned with Clustal Omega Multiple Sequence Alignment program and Percent Identity Matrices were derived. Phylogenetic analyses to elucidate evolutionary relationships between sequences were conducted with the neighbor-end joining method through the Molecular Evolutionary Genetics Analysis (MEGAX) software, developed by the Institute of Molecular Evolutionary Genetics at Pennsylvania State University. Subsequent network analyses of the resistance gene, vanB, within E. faecium were derived from ScanProsite and InterPro. RESULTS: We observed the highest nucleotide sequence similarity of vanA regions within strains of E. faecium (100%) and E. faecalis (100%). Between Enterococcus genera, we continued to observe high sequence conservation for vanA and vanB, up to 99.9% similarity. Phylogenetic tree analyses suggest rapid acquisition of these determinants between strains within vanA and vanB, particularly between strains of Enterococcus genera, which may be indicative of horizontal gene transfer. Within E. faecium, Adenosine 5’-Triphosphate (ATP)-Grasp and D-ala-D-ala ligase (Ddl) were found as conserved domains of vanA and vanB. We additionally found that there is notable sequence conservation, up to 66.67%, between resistomes against vancomycin and streptomycin among E. faecium. CONCLUSION: Resistance genes against vancomycin have highly conserved sequences between strains of Enterococcus bacteria. These conserved sequences within vanA and vanB encode for ATP-Grasp and Ddl motifs, which have functional properties for maintaining cell wall integrity. High sequence conservation is also observed among resistance genes against penicillin and streptomycin, which can inform future drug targets for broader spectrum therapies. Veterinary World 2022-10 2022-10-13 /pmc/articles/PMC9682389/ /pubmed/36425127 http://dx.doi.org/10.14202/vetworld.2022.2407-2413 Text en Copyright: © Memili, et al. https://creativecommons.org/licenses/by/4.0/Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Memili, Aylin
Kutchy, Naseer
Braimah, Olubumi A.
Morenikeji, Olanrewaju B.
Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci
title Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci
title_full Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci
title_fullStr Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci
title_full_unstemmed Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci
title_short Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci
title_sort evolutionary conservation of motifs within vana and vanb of vancomycin-resistant enterococci
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682389/
https://www.ncbi.nlm.nih.gov/pubmed/36425127
http://dx.doi.org/10.14202/vetworld.2022.2407-2413
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