Beta-lactamase (BL) (BL)

Beta-lactamases are a diverse family of enzymes produced by bacteria like Pseudomonas aeruginosa to confer resistance against beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems (Bush & Bradford, 2019, Nat Rev Microbiol). These enzymes function by hydrolyzing the four-atom beta-lactam ring, rendering the antibiotic ineffective before it can reach its target, the penicillin-binding proteins (Papp-Wallace et al., 2020, Front Microbiol). In P. aeruginosa, resistance is often driven by the inducible chromosomal AmpC cephalosporinase, as well as acquired resistance genes such as metallo-beta-lactamases (e.g., VIM, IMP) and extended-spectrum beta-lactamases (CDC, 2019, Antibiotic Resistance Threats). Targeting these enzymes with beta-lactamase inhibitors, such as avibactam or relebactam, is a primary therapeutic strategy to restore the efficacy of co-administered antibiotics (StatPearls, 2023, Pseudomonas Aeruginosa). This is particularly critical in treating healthcare-associated infections, such as ventilator-associated pneumonia and bloodstream infections, where multi-drug resistant Pseudomonas is prevalent (WHO, 2024, Fact Sheets). The clinical challenge is compounded by the ability of P. aeruginosa to upregulate these enzymes in response to antibiotic exposure, necessitating the use of potent, stable inhibitors (Papp-Wallace et al., 2020, Front Microbiol).

Other names

AmpC cephalosporinaseMetallo-beta-lactamaseCarbapenemasePenicillinaseCephalosporinaseExtended-spectrum beta-lactamase (Bush & Bradford, 2019, Nat Rev Microbiol)

Beta-lactamase inhibitors bind to the active site of the enzyme—either through reversible or irreversible covalent modification—thereby preventing the enzyme from degrading the beta-lactam ring of partner antibiotics (Bush & Bradford, 2019, Nat Rev Microbiol).