Evolutionary conservation of motifs within and 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 sequences and their evolutionary pathways among vancomycin-resistant species such as and .

Materials And Methods: We retrieved a total of 26 complete amino acid and nucleotide sequences of resistance determinant genes against vancomycin ( and , streptomycin (aac-aah), and penicillin () from the publicly available genetic sequence database, GenBank. The sequences were comprised of bacteria classified under the genera of , , , , and . 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, , within were derived from ScanProsite and InterPro.

Results: We observed the highest nucleotide sequence similarity of regions within strains of (100%) and (100%). Between genera, we continued to observe high sequence conservation for and , up to 99.9% similarity. Phylogenetic tree analyses suggest rapid acquisition of these determinants between strains within and , particularly between strains of genera, which may be indicative of horizontal gene transfer. Within , Adenosine 5'-Triphosphate (ATP)-Grasp and D-ala-D-ala ligase (Ddl) were found as conserved domains of and . We additionally found that there is notable sequence conservation, up to 66.67%, between resistomes against vancomycin and streptomycin among .

Conclusion: Resistance genes against vancomycin have highly conserved sequences between strains of bacteria. These conserved sequences within and 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.