Acquired Carbapenem-Hydrolyzing β-Lactamases and their Genetic Support - An Update

Carbapenem-hydrolyzing β-lactamases of several Ambler molecular classes have been reported as the source of acquired β-lactam antibiotic resistance in Gram negative bacteria. The metallo-enzymes of Ambler class B are the most prevalent enzymes in this case. These clavulanic-acid resistant enzymes have a large spectrum of hydrolysis including penicillins, cephalosporins (third and fourth generations), carbapenems but not monobactams. They are responsible for acquired resistance in several Gram negative species of clinical relevance in human medicine. IMP-1 was the first reported as acquired in Japan, mostly from Serratia marcescens and Pseudomonas aeruginosa isolates, and has been detected in Europe recently. Several variants of IMP-1 (IMP-2 to -13) have been characterized, possessing 85 to 99% amino acid identity, mostly from P. aeruginosa isolates. In addition, VIM-1 to -7 β-lactamases have also been described, first in Europe (Italy, France, and Greece) and now in Korea, Japan and also USA. The VIM series shares 30% amino acid identity with the IMP-series. Most of these class B enzymes have genes that are integron- and plasmid-located. Recently, another class B enzyme, SPM-1, has been identified from P. aeruginosa isolates in Brazil. This enzyme is weakly related to the others whereas sharing similar biochemical properties. The common region CR4 transposable element is likely involved in its acquisition. Finally, a few Ambler class A (SME-1, NMC-A, IMI-1/-2, KPC-1/-2) and class D (OXA-23 to - 27, OXA-40 and OXA-48) b-lactamases involved in carbapenem hydrolysis have been reported also from rare Gramnegative isolates. This review underlines the worldwide spread of carbapenem-hydrolyzing b-lactamases as representing an important threat for efficacy of antibiotics in the near future.