Lysine metabolism pathway as a target for drug repurposing: In silico approach against carbapenem-resistant Klebsiella pneumoniae

Abstract

Klebsiella pneumoniae (Kp) is a pathogenic bacterium known for its capacity to induce severe infections in humans, posing a significant threat to public health. Its resistance profile, particularly against carbapenem antibiotics, presents formidable challenges in clinical management. In response, a research endeavor was undertaken to discern prospective therapeutic targets against this pathogen. The investigation focused on delineating pivotal proteins involved in Host-Pathogen Interactions (HPIs) essential for the survival of Kp, thereby serving as potential targets for drug intervention. Through a careful screening process encompassing 438 proteins, 16 candidates were identified, prioritized based on criteria such as non-homology, essentiality, and druggability. Among these, 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase (DapD), instrumental in lysine metabolism, emerged as a promising candidate for further scrutiny as a drug target against K. pneumoniae. Subsequently, employing virtual screening and molecular docking techniques, the study evaluated the 9214-compound FDA library to pinpoint potential drug candidates targeting the DapD protein. Ultimately, 15 compounds exhibiting promise were identified, suggesting the prospect of repurposing these agents for the treatment of Kp infections. This research delineates a promising step in the quest for novel therapeutics against K. pneumoniae, signifying a potential paradigm shift in combating this resilient bacterial strain. The findings hold promise for the development of more efficacious and safer antimicrobial agents, thereby addressing the pressing clinical need posed by antibiotic-resistant pathogens.