A computational exploration of whole genome sequences of Klebsiella pneumoniae ST16 for beta-lactam resistance and the discovery of NDM-1 resistance gene inhibitor

Abstract

Antibiotic resistance is a growing concern in healthcare and medicine. This research was carried out to analyze whole genome sequences of Klebsiella pneumoniae ST16 with the goal of identifying genes that cause resistance to antibiotics and find potential bioactive compounds that can inhibit their growth. The study discovered genes that contribute to resistance against types of antibiotics such as macrolides, fluoroquinolones, aminoglycosides, sulphonamides, rifampicin, trimethoprim, and beta-lactams. Notable genes identified include blaTEM 1B, blaCTX M 15, and blaNDM-1. Furthermore, changes were observed in the acrR, ompK36, and gyrA genes, along with alterations in the corresponding acids, which are associated with resistance. The analysis also examined the alleles at each locus and found that the FIA locus had a new allele. Molecular docking results revealed that baicalein showed docking scores of −7.7 kcal/mol when binding with New Delhi Metallo 1 (NDM-1) related to beta-lactams. The RMSD plot demonstrated behavior for both Baicalein and Adapalene complexes of NDM-1 over a 50 ns simulation period. However, the higher Rg value for the drug-protein complex (NDM-1 Beta-Lactamase 1-Adapalene) indicates it may be slightly unstable in interaction compared to our test compound-protein complex (NDM-1 Beta-Lactamase 1-Baicalein). Summarily, the study offers information about how antibiotic resistance works against the NDM-1 gene and its role in beta-lactam resistance based on analysis which reveals that beyond baicalein, other excellent bioactive (taxifolin, and ellagic acid) strongly bind to the NDM 1 domain and can be further investigated experimentally.

Keywords

• Whole genome analysis
• Molecular docking
• Molecular dynamics simulation
• Antimicrobial resistance
• NDM-1
• Klebsiella pneumonia