Class A beta-lactamases and penicillin-binding proteins in Acinetobacter species (Class A BLs and PBPs (Acinetobacter))

This target profile represents a critical dual-mechanism approach for treating infections caused by Acinetobacter species, particularly Acinetobacter baumannii (Papp-Wallace et al., 2023). Class A beta-lactamases are serine-based enzymes produced by these bacteria that hydrolyze and inactivate various beta-lactam antibiotics, including penicillins and cephalosporins (Bush & Bradford, 2020). Penicillin-binding proteins (PBPs), specifically PBP1a, PBP1b, and PBP3, are essential membrane-associated enzymes involved in the final stages of peptidoglycan synthesis, which is necessary for maintaining bacterial cell wall integrity (Penwell et al., 2015). In Acinetobacter, certain drugs like sulbactam act as both a beta-lactamase inhibitor and a direct antibacterial agent by binding to these specific PBPs (Penwell et al., 2015). The combination of PBP-targeting agents with novel beta-lactamase inhibitors like durlobactam restores antibiotic efficacy by protecting the drug from enzymatic degradation by Class A, C, and D enzymes (Papp-Wallace et al., 2023). This synergistic strategy is vital for addressing multi-drug resistant (MDR) Acinetobacter infections, which are often associated with high mortality rates in hospital settings. Targeting these proteins simultaneously overcomes the primary resistance mechanisms employed by the pathogen, such as enzymatic inactivation and target site modification. Clinical focus on these targets has led to the development of specialized therapies like sulbactam-durlobactam, specifically designed for carbapenem-resistant Acinetobacter baumannii (CRAB).

Other names

Ambler Class A beta-lactamasesPenicillin-binding proteinsPBPsSerine beta-lactamasesAcinetobacter baumannii PBPsPBP1aPBP1bPBP3ftsI

Inhibition of bacterial cell wall synthesis through binding to penicillin-binding proteins (PBPs) and simultaneous inhibition of Class A beta-lactamases to prevent antibiotic degradation (Penwell et al., 2015; Papp-Wallace et al., 2023).