New CTX-M Group Conferring β-Lactam Resistance: A Compendium of Phylogenetic Insights from Biochemical, Molecular, and Structural Biology

SIMPLE SUMMARY: CTX-M β-lactamases are a growing group among extended-spectrum β-lactamases (ESBLs), not only in number, diversity, and functional kinetics. Until now, it has been well-accepted five main clusters within CTX-M β-lactamases. These canonical clusters are CTX-M-1, CTX-M-2, CTX-M-8, CTX-M-9, and CTX-M-25. In the present study, we propose a new sixth cluster, CTX-M-151. ABSTRACT: The production of extended-spectrum β-lactamases (ESBLs) is the main defense mechanism found in Gram negative bacteria. Among all the ESBLs, the CTX-M enzymes appear as the most efficient in terms of dissemination in different epidemiological contexts. CTX-M enzymes exhibit a striking plasticity, with a large number of allelic variants distributed in several sublineages, which can be associated with functional heterogeneity of clinical relevance. This observational analytical study provides an update of this family, currently with more than 200 variants described, from a phylogenetic, molecular, and structural point of view through homology in amino acid sequences. Our data, combined with described literature, provide phylogenetic and structural evidence of a new group. Thus, herein, we propose six groups among CTX-M enzymes: the already stablished CTX-M-1, CTX-M-2, CTX-M-8, CTX-M-9, and CTX-M-25 clusters, as well as CTX-M-151 as the new cluster.