Cracking the Code of Antibiotic Resistance OF Klebsiella pneumoniae ST16: A Computational Exploration of Whole Genome Sequences for Beta-lactam Resistance and the Discovery of NMD-1 Resistance Gene Inhibitor

Abstract

Antibiotic resistance is a growing concern in the field of healthcare and medicine. This research project involves an exploration of the whole genome sequences of Klebsiella pneumoniae ST16 from NCBI database with the aim of identifying resistance gene and potentially discovering its inhibitor. The study revealed the existence of several resistance genes to various classes of antibiotics, including macrolides, fluoroquinolones, aminoglycosides, sulphonamides, rifampicin, trimethoprim, and beta-lactams. Among these, blaTEM-1B, blaCTX-M-15, and blaNDM-1 were identified. Additionally, mutations were observed in the genes acrR, ompK36, and gyrA, along with changes in the corresponding amino acids, which are linked to resistance to different antibiotics. This analysis also identified the alleles present in each locus, with FIA having a novel allele, the molecular docking results indicate that Baicalein exhibited the highest docking scores of -7.7 respectively, indicating their strong binding affinity to the NDM-1 found to be associated with beta-lactams. The RMSD plot showed that both the Baicalein and Adapalene complexes of NDM-1 exhibited stable behavior over the 50 ns simulation period. However, the slightly higher Rg of the New Delhi Metallo-Beta-Lactamase 1-Adapalene complex indicates that this complex may be slightly more flexible than the New Delhi Metallo-Beta-Lactamase 1-Baicalein complex. In conclusion, the study provides valuable insights into the mechanisms of antibiotic resistance, particularly the role of the NDM-1 gene in beta-lactam resistance. Furthermore, the molecular docking analysis identified Baicalein, Taxifolin, and Ellagic acid as the top three bioactive compounds that exhibited strong binding affinity to the NDM-1 domain.