Exploring the action of new FimH inhibitors against CTX–15 enzyme by enzoinformatics approach: A plausible arsenal against drug-resistant uropathogenic bacterial strains

Abstract

Purpose: To explore the potency of FimH inhibitors against CTX-M β-lactamase enzyme type 15, in view of the increasing prevalence of CTX-M 15 in uropathogenic strains which has reduced the treatment options to minimal. Method: FimH inhibitors were targeted against CTXM-15 by a molecular docking approach. Thereafter, the best ligand-target confirmation was selected and analyzed using LIGPLOT+ Version v.2.1. The hydrophobic and hydrogen bonding among the catalytic site amino acids of CTXM-15 and the FimH inhibitors were analyzed and 3-D structures were converted into 2-D images by LIGPLOT algorithm. Results: Out of all the FimH inhibitors tested, 3′-chloro-4′- (α-D-mannopyranosyloxy) biphenyl-4-carbonitrile, para-biphenyl-2-methyl-3′-methylamidemannoside, para-biphenyl-2-methyl-3′,5′dimethylamide-α-D-mannoside, and thiazolylamino mannoside exhibited better interaction with the CTX-M 15 active site than the positive control avibactam. Moreover, in CTX-M 15, the amino acid residues, Ser70, Tyr105, Ser130, Asn132, Thr216, Thr235, Gly236, and Ser237 were commonly interacting with these FimH inhibitors as well as avibactam. Conclusion: The predicted findings suggest that these FimH inhibitors could be explored as potential CTX-M 15 inhibitors to cope-up with resistance issues of uropathogenic bacteria in the form of an alternate strategy.