Evolution of Drug Resistance: Insight on TEM β-Lactamases Structure and Activity and β-Lactam Antibiotics
Since the discovery of the first penicillin bacterial resistance to β-lactam antibiotics has spread and evolved
promoting new resistances to pathogens. The most common mechanism of resistance is the production of β-lactamases
that have spread thorough nature and evolve to complex phenotypes like CMT type enzymes. New antibiotics have been
introduced in clinical practice, and therefore it becomes necessary a concise summary about their molecular targets,
specific use and other properties. β-lactamases are still a major medical concern and they have been extensively studied
and described in the scientific literature. Several authors agree that Glu166 should be the general base and Ser70 should
perform the nucleophilic attack to the carbon of the carbonyl group of the β-lactam ring. Nevertheless there still is
controversy on their catalytic mechanism. TEMs evolve at incredible pace presenting more complex phenotypes due to
their tolerance to mutations. These mutations lead to an increasing need of novel, stronger and more specific and stable
antibiotics. The present review summarizes key structural, molecular and functional aspects of ESBL, IRT and CMT TEM
β-lactamases properties and up to date diagrams of the TEM variants with defined phenotype. The activity and structural
characteristics of several available TEMs in the NCBI-PDB are presented, as well as the relation of the various mutated
residues and their specific properties and some previously proposed catalytic mechanisms.
Keywords: Antibiotics, β-lactamases, CMT, ESBL, IRT, TEM.
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