Evolutionary convergence of enzymatic and target-mediated resistance in Escherichia coli: from CTX-Ms to PBP-3...

Antimicrobial-resistant (AMR) Escherichia coli has undergone significant transformations over the past three decades. Largely susceptible to the fluoroquinolones (FQs) and cephalosporins (cephs) during the 1990s, E. coli has evolved into major multidrug-resistant (MDR) pathogens through the sequential acquisition of chromosomal target modifications and plasmid-mediated β‑lactamases.

This evolution consisted of two major waves of convergence: an initial merger of quinolone resistance-determining regions (QRDR) mutations (FQ-R) with CTX-M β‑lactamases (ceph-R) during the 2000s, followed by combining penicillin-binding proteins (PBP)‑3 insertions (YRIN, YRIK) with NDMs (carbapenem-R) during the 2010s. These AMR mergers were largely driven by MDR high-risk clones, notably ST131 (QRDR mutations + CTX-M-15) and ST410/ST167 (PBP3 insertions + NDM-5). MDR strains harboring YRIN and YRIK exhibit reduced susceptibilities to last-line therapies, such as newer β-lactam/β-lactamase inhibitors (especially those containing aztreonam, cefepime, and ceftazidime).

These developments underscore the remarkable adaptability of E. coli under antimicrobial pressure and highlight the need for improved surveillance, diagnostics, and therapeutic strategies to combat the ongoing expansion of MDR strains.