TITLE:
Metallo-β-Lactamases: A Major Threat to Human Health
AUTHORS:
Emer K. Phelan, Manfredi Miraula, Christopher Selleck, David L. Ollis, Gerhard Schenk, Nataša Mitić
KEYWORDS:
Antibiotic Resistance, β-Lactam Antibiotics, Metallo-β-Lactamases, Reaction Mechanism, Metal Ion Binding
JOURNAL NAME:
American Journal of Molecular Biology,
Vol.4 No.3,
July
16,
2014
ABSTRACT: Antibiotic
resistance is one of the most significant challenges facing global healthcare.
Since the 1940s, antibiotics have been used to fight infections, initially with
penicillin and subsequently with various derivatives including cephalosporins,
carbapenams and monobactams. A common characteristic of these antibiotics is the
four-memberedβ-lactam ring. Alarmingly,
in recent years an increasing number of bacteria have become resistant to these
antibiotics. A major strategy employed by these pathogens is to use
Zn(II)-dependent enzymes, the metallo-β-lactamases
(MBLs), which hydrolyse theβ-lactam
ring. Clinically useful MBL inhibitors are not yet available. Consequently,
MBLs remain a major threat to human health. In this review biochemical
properties of MBLs are discussed, focusing in particular on the interactions
between the enzymes and the functionally essential metal ions. The precise
role(s) of these metal ions is still debated and may differ between different
MBLs. However, since they are required for catalysis, their binding site may
present an alternative target for inhibitor design.