Beta-lactamases are bacterial enzymes which impart resistance against
β-lactam-antibiotics. CTX-Ms are the β-lactamases that target cephalosporin antibiotics
(e.g. cefotaxime and ceftazidime) while SME-1, KPC-2, IMI-1 and SFC-1 target carbapenems.
Clavulanic acid, sulbactam and tazobactam are traditional β-lactamase inhibitors while
LN1-255 and NXL-104 whereas novel inhibitors, inhibiting the activity of these enzymes.
Studying the binding pattern of these drugs is helpful in predicting the versatile
inhibitors for betalactamases. The aims of the study were: describing the mode of
interaction of CTX-M (modeled from the
blaCTX-M
gene of this
study) and the said carbapenemases with their respective target drugs and inhibitors and
to perform an
in silico
comparison of the efficacies of traditional and
novel β-lactamase-inhibitors based on fitness score. The
blaCTX-M
marker was PCR-amplified from plasmid DNA of E.
coli strain isolated from community-acquired urinary tract infection.
E.
coli
C600 cells (harboring cloned
blaCTX-M
) were
found positive for extended-spectrum-β-lactamase (ESBL) production by the
double-disk-synergy test. The three dimensional structures of CTX-M-15, SME-1 and IMI-1
were predicted by Swiss Model Server. The interaction between selected structures and
inhibitors was performed by GOLD 5.0. On the basis of the docking score and binding
pattern, we conclude that compound LN1-255 followed by tazobactam is best inhibitor
against all the selected target enzymes as compared to clavulanate, sulbactam and NXL-104.
Five conserved amino acids, Ser70, Ser130, Lys235, Thr236 and Gly237 were found crucial in
stabilizing the complexes through hydrogen bonding and hydrophobic interactions.