São Paulo metallo-beta-lactamase (SPM-1) (SPM-1)

São Paulo metallo-beta-lactamase (SPM-1) is a Class B1 metallo-beta-lactamase (MBL) that serves as a critical mechanism of high-level antibiotic resistance in Gram-negative bacteria, particularly Pseudomonas aeruginosa [2, 7]. First identified in São Paulo, Brazil, it has become a dominant carbapenemase in South America and poses a significant global health threat due to its ability to be transmitted via mobile genetic elements like ISCR4 [10, 11]. As a zinc-dependent enzyme, SPM-1 catalyzes the hydrolysis of the amide bond in the four-membered beta-lactam ring, effectively inactivating a wide range of antibiotics including penicillins, cephalosporins, and carbapenems [1, 15]. Unlike serine-beta-lactamases, SPM-1 is not inhibited by conventional clinical inhibitors such as clavulanic acid or tazobactam, and it possesses unique structural features, including a 23-residue loop, that complicate the development of universal MBL inhibitors [2, 4]. Consequently, infections involving SPM-1-producing strains are associated with limited therapeutic options and high mortality rates, necessitating the development of novel metallo-enzyme inhibitors or alternative antimicrobial strategies like cefiderocol [12, 18].

Other names

Sao Paulo metallo-beta-lactamaseblaSPM-1Class B1 metallo-beta-lactamaseSPM-1 MBL

Inhibition of the zinc-dependent hydrolytic activity to restore the efficacy of beta-lactam antibiotics.