Beta-lactamase (BLA) (BLA)

Beta-lactamases are enzymes produced by bacteria that provide resistance to beta-lactam antibiotics, including penicillins, cephalosporins, cephamycins, and carbapenems (Bush & Bradford, 2016). These enzymes function by hydrolyzing the cyclic amide bond of the beta-lactam ring, which inactivates the antibiotic and prevents it from binding to its target penicillin-binding proteins (StatPearls, 2023). They are categorized into four main Ambler classes (A, B, C, and D) based on their amino acid sequences; classes A, C, and D are serine-beta-lactamases, while class B enzymes are zinc-dependent metallo-beta-lactamases (Tooke et al., 2019). The emergence of extended-spectrum beta-lactamases (ESBLs) and carbapenemases has significantly complicated the treatment of Gram-negative bacterial infections (CDC, 2019). To overcome this resistance, beta-lactamase inhibitors like clavulanic acid, tazobactam, and avibactam are co-administered with antibiotics to neutralize the enzymes and restore antibiotic efficacy (Drawz & Bonomo, 2010). These inhibitors work by either acting as suicide substrates that covalently bond to the enzyme or by non-covalently occupying the active site (Bush, 2018). The rapid evolution and horizontal gene transfer of beta-lactamase genes among bacterial populations pose a major challenge to modern medicine (Munita & Arias, 2016). Monitoring for these enzymes through molecular and phenotypic testing is essential for guiding appropriate antimicrobial therapy (Tamma et al., 2021).

Other names

PenicillinaseCephalosporinaseCarbapenemaseMetallo-beta-lactamaseSerine beta-lactamaseBeta-lactam hydrolase

Inhibition of the enzyme's catalytic activity through covalent or non-covalent binding to the active site, preventing antibiotic hydrolysis (StatPearls, 2023).