Computational Annotation and Experimental Validation of Hypothetical Proteins as Novel Drug Targets in Klebsiella pneumoniae HS11286
Year: 2026
Type: article
Abstract: Background: Klebsiella pneumoniae is a significant pathogen causing severe infections, especially among immunocompromised individuals. The emergence of Multidrug-Resistant (MDR) strains has heightened public health concerns. This study investigates the potential of Hypothetical Proteins (HPs) in K. pneumoniae HS11286 as new drug targets through functional annotation and experimental validation. Materials and Methods: We utilized bioinformatics tools to analyze 974 HPs for their functions, subcellular localization, and drug target potential. Techniques such as subtractive genomics and virulence prediction were applied to identify essential and non-toxic proteins. Structural modeling and druggability assessments were conducted on selected HPs. The role of these proteins in antibiotic resistance was experimentally validated using Polymyxin B and the PmrD protein. Results: From the 974 HPs, 732 were successfully classified functionally, with 30 identified as potential drug targets. Experiments revealed that PmrD significantly increases K. pneumoniae's resistance to Polymyxin B, highlighting its involvement in resistance mechanisms. Conclusion: Our study offers a detailed functional annotation of HPs in K. pneumoniae HS11286 and uncovers several promising drug targets. These findings are crucial for developing new therapies against MDR K. pneumoniae. Future work should focus on further validating these targets through molecular docking and high-throughput screening for potential clinical applications.
Authors: Yanping Li, Suresh Kumar, Lihu Zhang
Language: English
Subfield: Drug Discovery
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W7224311780