In Silico Study of Ceftazidime and Piperacillin Against Penicillin-Binding Protein 2, Beta-Lactamase (OXA-1 and SHV-28) of Klebsiella pneumoniae U25

Abstract

Background: To combat the action of beta-lactams, Klebsiella pneumoniae launches the enzymatic action by
producing beta-lactamases to destruct the activity of ceftazidime and piperacillin. Objective: In our research, we
want to know the action of ceftazidime and piperacillin on penicillin-binding protein2 (PBP2) and also does it have
any interactions with beta-lactamases (OXA1 and SHV-28). Our idea is to prevent the action of beta-lactamases on
ceftazidime and piperacillin. Hence, we have modified the beta-lactam core structures of ceftazidime and piperacillin
and done the comparative docking interaction studies. Materials and Methods: K. pneumoniae U25 has been selected
for the comparative docking analysis study with ceftazidime and piperacillin antibiotics by modifying its structures
and targeting them against PBP2 and beta-lactamases (OXA-1 and SHV-28). Results: Our docking analysis revealed
that ceftazidime and modified ceftazidime are forming hydrogen bonds, but piperacillin and modified piperacillin are
showing hydrophobic interactions with an active site serine residue (Ser316) of PBP2 responsible for the transpeptidase
activity in K. pneumoniae U25. Protective action by beta-lactamases (OXA-1 and SHV-28) to K. pneumoniae U25
against beta-lactam antibiotics is also revealed through our study by docking interactions of Ser71 of OXA-1 and
Ser66 of SHV-28 with the ceftazidime, modified ceftazidime, piperacillin, and modified piperacillin.