Bacterial Class D serine β-lactamase and metallo-β-lactamase (OXA and MBL)

Bacterial Class D serine β-lactamases and metallo-β-lactamases (MBLs) are critical enzymes that mediate resistance to a broad spectrum of β-lactam antibiotics, including carbapenems, in Gram-negative pathogens (Bush & Jacoby, 2010, PMID: 20008551). Class D enzymes, or OXA-type β-lactamases, utilize a serine-based mechanism to hydrolyze antibiotics, while MBLs (Class B) are zinc-dependent enzymes that use metal ions to facilitate the same reaction (Palzkill, 2013, PMID: 23317014). These enzymes are major drivers of multi-drug resistance in ESKAPE pathogens like Klebsiella pneumoniae and Acinetobacter baumannii, often leading to severe healthcare-associated infections (Bonomo, 2017, PMID: 28404525). Therapeutic strategies involve the development of β-lactamase inhibitors, such as avibactam for certain Class D enzymes and novel boronate-based inhibitors like taniborbactam that target both classes (Hecker et al., 2020, PMID: 32433183). By inhibiting these enzymes, these drugs restore the efficacy of partner antibiotics, providing a vital defense against life-threatening infections. The global spread of genes encoding these enzymes, such as blaOXA-48 and blaNDM-1, remains a significant challenge for modern medicine. Clinical management often requires rapid diagnostic testing to identify the specific resistance mechanism present in a patient infection. Ongoing research focuses on expanding the spectrum of inhibitors to cover emerging variants and minimizing potential side effects associated with metal chelation.

Other names

Class D beta-lactamaseClass B beta-lactamaseOXA-type carbapenemaseZinc-dependent beta-lactamaseMetallo-beta-lactamaseAmbler Class B and Class D beta-lactamases

Inhibition of bacterial β-lactamase enzymes to prevent the degradation of co-administered β-lactam antibiotics, thereby restoring their bactericidal activity.