Background & Objective: Pseudomonas aeruginosa shows resistance to a large number of
antibiotics, including carbapenems and third generation cephalosporin. According to the World Health
Organization global report published in February 2017, Pseudomonas aeruginosa is on the priority list
among resistant bacteria, for which new antibiotics are urgently needed. Peptidoglycan serves as a
good target for the discovery of novel antimicrobial drugs.
Methods: Biosynthesis of peptidoglycan is a multi-step process involving four mur enzymes. Among
these enzymes, UDP-N-acetylmuramate-L-alanine ligase (MurC) is considered to be an excellent target
for the design of new classes of antimicrobial inhibitors in gram-negative bacteria.
Results: In this study, a homology model of Pseudomonas aeruginosa MurC ligase was generated and
used for virtual screening of chemical compounds from the ZINC Database. The best screened inhibitor
i.e. N, N-dimethyl-2-oxo-2,3-dihydro-1H-1,3-benzodiazole-5-sulfonamide was then validated experimentally
through inhibition assay.
Conclusion: The presented results based on combined computational and in vitro analysis open up
new horizons for the development of novel antimicrobials against this pathogen.