Serine beta-lactamase (SBL) (SBL)

Serine beta-lactamases (SBLs) are a diverse group of enzymes produced by bacteria, particularly Gram-negative species, that serve as a primary mechanism of resistance against beta-lactam antibiotics [1, 6, 10]. These enzymes are classified into Ambler classes A, C, and D and are characterized by a conserved serine residue in the active site that facilitates the hydrolytic cleavage of the four-membered beta-lactam ring [2, 13, 17]. By inactivating antibiotics such as penicillins, cephalosporins, and carbapenems, SBLs prevent these drugs from inhibiting cell wall synthesis, thereby allowing the bacteria to survive in the presence of antimicrobial agents [8, 11, 18]. SBLs are frequently encoded on mobile genetic elements, such as plasmids and transposons, which enables their rapid dissemination across different bacterial genera and contributes to the global crisis of multidrug resistance [10, 15, 16]. In clinical practice, SBLs are targeted by beta-lactamase inhibitors (BLIs) like clavulanic acid, tazobactam, and avibactam, which are administered in combination with beta-lactam antibiotics to restore their efficacy [7, 12, 14]. These inhibitors work by binding to the active-site serine, either as suicide substrates or through reversible covalent bonding, effectively neutralizing the enzyme's activity [13, 17, 18]. Despite the success of these combinations, the continuous evolution of SBLs has led to the emergence of variants that can evade current inhibitors, such as KPC carbapenemases and inhibitor-resistant TEM enzymes [1, 11, 14]. Consequently, the development of next-generation inhibitors and the monitoring of SBL-mediated resistance remain critical priorities for infectious disease management and drug development [10, 16].

Other names

Ambler Class A beta-lactamaseAmbler Class C beta-lactamaseAmbler Class D beta-lactamaseActive-site serine beta-lactamaseSBLPenicillinaseCephalosporinaseCarbapenemase (serine-type)

Serine beta-lactamases catalyze the hydrolysis of the beta-lactam ring in antibiotics through a two-step mechanism involving the formation of a covalent acyl-enzyme intermediate with an active-site serine residue, followed by deacylation to release the inactive antibiotic [6, 9, 10, 18]. Beta-lactamase inhibitors target these enzymes by binding to the active site, either acting as suicide substrates that permanently inactivate the enzyme or forming stable, slowly-reversing covalent complexes that prevent the enzyme from degrading co-administered antibiotics [7, 13, 14, 17].