Abstract
Klebsiella pneumoniae is an opportunistic multidrug-resistant bacterial pathogen responsible for various health care-associated infections. The prediction of proteins that are essential for the survival of bacterial pathogens can greatly facilitate the drug development and discovery pipeline toward target identification. To this end, the present study reports a comprehensive computational approach integrating bioinformatics and systems biology-based methods to identify essential proteins of K. pneumoniae involved in vital processes. From the proteome of this pathogen, we predicted a total of 854 essential proteins based on sequence, protein-protein interaction (PPI) and genome-scale metabolic model methods. These predicted essential proteins are involved in vital processes for cellular regulation such as translation, metabolism, and biosynthesis of essential factors, among others. Cluster analysis of the PPI network revealed the highly connected modules involved in the basic functionality of the organism. Further, the predicted consensus set of essential proteins of K. pneumoniae was evaluated by comparing them with existing resources (NetGenes and PATHOgenex) and literature. The findings of this study offer guidance toward understanding cell functionality, thereby facilitating the understanding of pathogen systems and providing a way forward to shortlist potential therapeutic candidates for developing novel antimicrobial agents against K. pneumoniae. In addition, the research strategy presented herein is a fusion of sequence and systems biology-based approaches that offers prospects as a model to predict essential proteins for other pathogens.
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