Phylogenetic Relationships and Structural Conservation of blaOXA-48-like Carbapenemase in Multispecies Clinical...

The global dissemination of carbapenem resistance is predominantly facilitated by plasmid-mediated carbapenemase genes, notably blaOXA-48-like genes. A comprehensive understanding of their evolutionary relationships and structural conservation is essential for monitoring their spread and informing therapeutic strategies. This study aimed to investigate the phylogenetic relationships and structural conservation of blaOXA-48-like carbapenemase genes in multiple Gram-negative bacterial species. We analysed blaOXA-48-like carbapenemase sequences obtained from a hospital in Pakistan and compared them with globally reported variants retrieved from GenBank. Carbapenemase gene sequences (blaOXA-48-like, blaNDM, and blaVIM) were analyzed using maximum-likelihood phylogenetics (MEGA11, Tamura-Nei model, 1000 bootstrap replicates). Comparative global sequences were retrieved from GenBank. Structural modeling of blaOXA-48-like genes was performed using SWISS-MODEL Workspace with the template PDB 3HBR, followed by validation using GMQE, QMEANDisCo, and Ramachandran plot analyses. Phylogenetic analysis revealed a tight clustering of blaOXA-48-like genes across A. baumannii, K. pneumoniae, and E. meningoseptica, showing high similarity to globally distributed plasmid-associated sequences. Structural modeling demonstrated strong conservation of the enzyme, with preserved catalytic residues (Ser70, Lys73, Ser118, Trp157, and Tyr211) and minimal structural deviation (RMSD < 0.3 Å). blaOXA-48-like carbapenemases exhibit strong phylogenetic conservation and structural stability across species and regions, consistent with the horizontal dissemination of blaOXA-48-like genes across bacterial hosts. These findings indicate that blaOXA-48-like carbapenemases have high evolutionary stability.