Molecular Characterization andIn SilicoAnalysis of Naturally Occurring TEM Beta-Lactamase Variants among PathogenicEnterobacteriaceaeInfecting Indian Patients

摘要

Cephalosporin resistance, particularly due toblaTEMencodedβ-lactamases, amongEnterobacteriaceaeis, though, an increasing public health problem in India; their circulating genetic variants remain unknown. The present study deals with determination ofblaTEMvariants among 134 pathogenicEnterobacteriaceaeof Indian origin. Their resistance profile against 3rd generation cephalosporins was determined. The presence ofblaTEMvariants among the bacterial plasmids was characterized by PCR followed by sequencing. Intergenic relations among the variants was determined by phylogenetic analysis.blaTEMprotein were modeled by Modeller9v5 and verified. The catalytic pockets were characterized, and their interaction with cephalosporins was analyzed using AutoDock tools. More than 87% of isolates showed cephalosporin resistance with ESBL production among 57.8% ofEscherichia coliand 50.6% ofklebsiella pneumoniae.blaTEM-1(84.21%),blaTEM-1like (3.94%),blaTEM-33(3.94%),blaTEM-116(3.94%),blaTEM-169(3.94%), andblaTEM-190(7.89%) were detected in 76 isolates. Four variants, namely,blaTEM-1like,blaTEM-33,blaTEM-169, andblaTEM-190, coexisted in 3 isolates. The largest catalytic pocket ofblaTEM-33explained its expanded activity towardsβ-lactam-β-lactamase inhibitor combinations. Molecular docking indicated differential resistance pattern ofblaTEMvariants.