Pseudomonas-derived cephalosporinase PDC-3 and PDC-88 (PDC-3/PDC-88)

Pseudomonas-derived cephalosporinase (PDC) variants PDC-3 and PDC-88 are chromosomally encoded Class C (AmpC) beta-lactamases produced by the opportunistic pathogen Pseudomonas aeruginosa [4, 6]. These enzymes function as serine-based hydrolases that provide resistance to a wide array of beta-lactam antibiotics, including penicillins and cephalosporins, by cleaving the amide bond of the beta-lactam ring [7, 13]. PDC-3 is one of the most frequently encountered clinical variants, while PDC-88 is a specialized "gain-of-function" variant featuring a two-residue deletion in the R2-loop (Thr289-Pro290) that significantly enhances its ability to hydrolyze fourth-generation cephalosporins like cefepime [1, 4]. The presence of these enzymes, particularly the extended-spectrum variants, is a major driver of multidrug resistance in clinical settings, often necessitating the use of advanced beta-lactam/beta-lactamase inhibitor (BL/BLI) combinations [5, 12]. Novel inhibitors such as taniborbactam and avibactam are designed to overcome this resistance by covalently binding to the enzyme's active site, thereby restoring the efficacy of partner antibiotics [1, 6, 8].

Other names

AmpC beta-lactamasePseudomonas-derived cephalosporinaseblaPDC-3blaPDC-88Class C beta-lactamasePDC-3PDC-88

These enzymes catalyze the hydrolysis of the beta-lactam ring in antibiotics, rendering them inactive [7, 13]. Beta-lactamase inhibitors like taniborbactam and avibactam target these enzymes by forming a stable covalent bond with the catalytic serine residue (S64), thereby preventing the degradation of co-administered antibiotics [4, 6, 8].