CTX-M Enzymes: Origin and Diffusion
CTX-M β-lactamases are considered a paradigm in the evolution of a resistance mechanism. Incorporation of different chromosomal blaCTX-M related genes from different species of Kluyvera has derived in different CTX-M clusters. In silico analyses have shown that this event has occurred at least nine times; in CTX-M-1 cluster (3), CTX-M-2 and CTX-M-9 clusters (2 each), and CTX-M-8 and CTX-M-25 clusters (1 each). This has been mainly produced by the participation of genetic mobilization units such as insertion sequences (ISEcp1 or ISCR1) and the later incorporation in hierarchical structures associated with multifaceted genetic structures including complex class 1 integrons and transposons. The capture of these blaCTX-M genes from the environment by highly mobilizable structures could have been a random event. Moreover, after incorporation within these structures, β-lactam selective force such as that exerted by cefotaxime and ceftazidime has fueled mutational events underscoring diversification of different clusters. Nevertheless, more variants of CTX-M enzymes, including those not inhibited by β-lactamase inhibitors such as clavulanic acid (IR-CTX-M variants), only obtained under in in vitro experiments, are still waiting to emerge in the clinical setting. Penetration and the later global spread of CTX-M producing organisms have been produced with the participation of the so-called "epidemic resistance plasmids" often carried in multi-drug resistant and virulent high-risk clones. All these facts but also the incorporation and co-selection of emerging resistance determinants within CTX-M producing bacteria, such as those encoding carbapenemases, depict the currently complex pandemic scenario of multi-drug resistant isolates. ; José María González-Alba is supported by fellow research contracts from the European Commission funded project PAR, HEALTH-2009-241476). The content and the scientific background of the manuscript were obtained in part from the European Commission funded projects (COBRA, LSHM-CT-2003-503335; TROCAR, HEALTH-F3-2008-223031; and PAR, HEALTH-2009-241476), the Spanish Ministry of Science and Innovation through Instituto de Salud Carlos III (research grant FIS-PI-080624) and the CIBERESP (research network in Epidemiology and Public Health, CB06/02/0053), and the Regional Government of Madrid [DeRemicrobiana Network (CAM.S-SAL-0246-2006)]. ; Peer reviewed ; Peer Reviewed