| Summary: | Despite the increasing evidence of the clinical impact of <i>Pseudomonas</i>-derived cephalosporinase (PDC) sequence polymorphisms, the molecular evolution of its encoding gene, <i>bla</i><sub>PDC</sub>, remains elusive. To elucidate this, we performed a comprehensive evolutionary analysis of <i>bla</i><sub>PDC</sub>. A Bayesian Markov Chain Monte Carlo phylogenetic tree revealed that a common ancestor of <i>bla</i><sub>PDC</sub> diverged approximately 4660 years ago, leading to the formation of eight clonal variants (clusters A–H). The phylogenetic distances within clusters A to G were short, whereas those within cluster H were relatively long. Two positive selection sites and many negative selection sites were estimated. Two PDC active sites overlapped with negative selection sites. In docking simulation models based on samples selected from clusters A and H, piperacillin was bound to the serine and the threonine residues of the PDC active sites, with the same binding mode for both models. These results suggest that, in <i>P. aeruginosa</i>, <i>bla</i><sub>PDC</sub> is highly conserved, and PDC exhibits similar antibiotic resistance functionality regardless of its genotype.
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