Isolation of ESBL-producing gram-negative bacteria and in silico inhibition of ESBLs by flavonoids

Abstract

Abstract Objective To evaluate nosocomial accounts of 426 extended spectrum β-lactamase (ESBL)-producing strains from 705 isolates of 9 pathogenic gram-negative bacteria in vitro. We analysed the genetic divergence of ESBLs by constructing a phylogenetic tree and modelled flavonoid inhibition of ESBLs with in silico molecular docking to determine effective control options. Methods Nine ESBL-producing bacteria were isolated from urine samples and their antibiograms were determined by the disc-diffusion method. Comparative models of the 9 ESBL enzymes were generated computationally using reference sequences, and validated by Ramachandran plots. Molecular docking with 11 flavonoids was conducted against the ESBL models. Results Isolated strains were floridly multidrug-resistant. From the docking study, the predicted minimum energy value of amikacin was −8.108 kcal/mol against the wild type TEM-1 ESBL of Acinetobacter baumannii , while the docking value against the mutant type Escherichia coli was −7.388 kcal/mol. The docking scores obtained corroborated the in vitro results showing that the antibiotic was incapable of controlling the ESBL of the mutant strain. Among 11 flavonoids tested against the mutant ESBL of E. coli , epigallocatechin 3-gallate and eriodictyol, with docking scores of −9.448 and −8.161 kcal/mol, respectively, were the most effective, with drug-likeness scores of 0.39 and 1.37, respectively, compared to 1.03 for amikacin. Conclusion Docking scores and drug-likeness scores indicated that flavonoids are compelling alternative antimicrobial agents that could serve as complementary therapy for newly arising ESBL-producing bacteria. Phylogenetic tree analysis elucidated the genetic relationship of the 9 ESBL serotypes.