Class A beta-lactamase (Class A BLA)

Class A beta-lactamases are a prominent family of bacterial enzymes that serve as a primary mechanism of resistance against beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems [1, 7]. These enzymes function as serine hydrolases, utilizing a conserved active-site serine residue to catalyze the nucleophilic attack and subsequent hydrolysis of the four-atom beta-lactam ring, thereby deactivating the antibiotic's ability to inhibit bacterial cell wall synthesis [4, 8]. The family is highly diverse and includes widely distributed narrow-spectrum penicillinases like TEM-1 and SHV-1, as well as clinically significant extended-spectrum beta-lactamases (ESBLs) and potent carbapenemases such as KPC [2, 5, 10]. Class A beta-lactamases are frequently encoded on mobile genetic elements like plasmids and transposons, facilitating their rapid horizontal spread among Gram-negative pathogens, particularly Enterobacterales [1, 3]. In clinical practice, these enzymes are the primary targets for beta-lactamase inhibitors, which are co-administered with antibiotics to neutralize the enzyme and restore the therapeutic efficacy of the antimicrobial treatment [9, 11].

Other names

Ambler class A beta-lactamaseSerine beta-lactamase class APenicillinaseExtended-spectrum beta-lactamase (ESBL)KPC carbapenemase

Beta-lactamase inhibitors function by binding to the active-site serine of the enzyme, either as suicide inhibitors that form an irreversible covalent bond (e.g., clavulanic acid, tazobactam) or as high-affinity reversible inhibitors (e.g., avibactam, vaborbactam), preventing the hydrolysis of co-administered beta-lactam antibiotics [11, 15].