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

Jacinta Mendonça,Ruben Fernandes,Sara Sá,Marco Oliveira,Cláudia Pereira,Carla Guedes,Pedro Barata,Carina Silva,Pilar Baylina,Gustavo Accioly

doi:10.3390/biology11020256

Abstract

Simple SummaryCTX-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.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.

Highlights

Penicillin, discovered by Alexander Fleming in 1928, represented a turning point for humanity, revolutionizing Medicine by significantly reducing the number of deaths from bacterial infections worldwide [1,2,3]
Considering that the epidemiology of CTX-M-type ESBLs is evolving rapidly, the objective of this paper is to provide a concise update on CTX-M-type β-lactamases, with a focus on aspects related to enzymatic properties, structural relationships, and phylogenetic significance of the CTX-M-type ESBLs, proposing a new group within CTX-M family
Perhaps it may be related to the fact that CTX-M enzymes exhibit a striking plasticity, with many allelic variants belonging to several sublineages

Summary

Introduction

Penicillin, discovered by Alexander Fleming in 1928, represented a turning point for humanity, revolutionizing Medicine by significantly reducing the number of deaths from bacterial infections worldwide [1,2,3]. The introduction of antimicrobial agents in clinical practice was followed by the gradual appearance of resistant bacterial strains, whose threat of dissemination constitutes a worrying reality in Public Health [4,5]. In this matter, it is estimated that approximately 25,000 patients die each year in the European Union because of infections caused by multidrug-resistant bacteria, and the associated costs are estimated circa 1.5 billion euros/per year) [6]. The production of β-lactamases is the predominant cause of resistance to β-lactam antibiotics in Gram-negative bacteria [1,8]. The introduction of expanded spectrum cephalosporins in clinical practice in the early 1980s represented a breakthrough for the treatment of infections caused by Enterobacteriaceae and other Gram-negative pathogens [12]

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