CTX-M-type β-lactamases: a successful story of antibiotic resistance

Production of extended-spectrum β-lactamases (ESBLs) is the principal mechanism of resistance to oxyimino-cephalosporins evolved by members of the family Enterobacteriaceae. Among the several ESBLs emerged among clinical pathogens, the CTX-M-type enzymes have proved the most successful in terms of promiscuity and diffusion in different epidemiological settings, where they have largely replaced and outnumbered other types of ESBLs. Originated by the capture and mobilization of chromosomal β-lactamase genes of strains of Kluyvera species, the blaCTX-M genes have become associated with a variety of mobile genetic elements that have mediated rapid and efficient inter-replicon and cell-to-cell dissemination involving highly successful enterobacterial lineages (e.g. Escherichia coli ST131 and ST405, or Klebsiella pneumoniae CC11 and ST147) to yield high-risk multiresistant clones that have spread on a global scale. The CTX-Mβ-lactamase lineage exhibits a striking plasticity, with a large number of allelic variants belonging in several sublineages, which can be associated with functional heterogeneity of clinical relevance. This review article provides an update on CTX-M-type ESBLs, with focus on structural and functional diversity, epidemiology and clinical significance.