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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Main Authors: Aylin Memili, Naseer Kutchy, Olubumi A. Braimah, Olanrewaju B. Morenikeji
Format: Article
Language:English
Published: Veterinary World 2022-10-01
Series:Veterinary World
Subjects:
Online Access:http://www.veterinaryworld.org/Vol.15/October-2022/6.pdf
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author Aylin Memili
Naseer Kutchy
Olubumi A. Braimah
Olanrewaju B. Morenikeji
author_facet Aylin Memili
Naseer Kutchy
Olubumi A. Braimah
Olanrewaju B. Morenikeji
author_sort Aylin Memili
collection DOAJ
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 doaj.art-fbf6c520d33f4dc8aac3ed88f88363cb2022-12-22T03:32:01ZengVeterinary WorldVeterinary World0972-89882231-09162022-10-0115102407241310.14202/vetworld.2022.2407-2413Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococciAylin Memili0https://orcid.org/0000-0003-1872-2098Naseer Kutchy1https://orcid.org/0000-0003-3125-4516Olubumi A. Braimah2Olanrewaju B. Morenikeji3https://orcid.org/0000-0003-2608-3302Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.Department of Anatomy, Physiology, Pharmacology, School of Veterinary Medicine, St. George's University, Grenada, West Indies.Division of Biological Health Sciences, University of Pittsburgh, Bradford, Pennsylvania, United States.Division of Biological Health Sciences, University of Pittsburgh, Bradford, Pennsylvania, United States.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.http://www.veterinaryworld.org/Vol.15/October-2022/6.pdfantibiotic resistancebioinformaticsenterococcusevolutionpublic health
spellingShingle Aylin Memili
Naseer Kutchy
Olubumi A. Braimah
Olanrewaju B. Morenikeji
Evolutionary conservation of motifs within vanA and vanB of vancomycin-resistant enterococci
Veterinary World
antibiotic resistance
bioinformatics
enterococcus
evolution
public health
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 antibiotic resistance
bioinformatics
enterococcus
evolution
public health
url http://www.veterinaryworld.org/Vol.15/October-2022/6.pdf
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AT olubumiabraimah evolutionaryconservationofmotifswithinvanaandvanbofvancomycinresistantenterococci
AT olanrewajubmorenikeji evolutionaryconservationofmotifswithinvanaandvanbofvancomycinresistantenterococci