Identification and characterization of potential druggable targets among Essential Hypothetical Proteins of A. baumannii

Abstract

Acinetobacter baumannii, a gram negative bacteria, has emerged as a critical pathogen responsible for nosocomial and other infections. A. baumannii exhibits resistance to a variety of antibiotic classes, emphasizing that new therapeutic targets are urgently needed. In A. baumannii, ATCC 179778, 458 genes have been identified as essential genes, indispensable for growth and survival of the pathogen. The functions of 47 proteins encoded by A.baumannii essential genes were found to be hypothetical and thus referred as essential hypothetical proteins (EHPs). The present study aims to carry out functional characterization of EHPs using bioinformatics tools/databases. Evaluation of physicochemical parameters, homology search against known proteins, domain analysis, subcellular localization analysis, 3D structure prediction and virulence prediction assisted us to characterize EHPs. They belong to different functional classes like enzymes, binding proteins, helicases, transporters, miscellaneous proteins and virulence factors. Around 47% of EHPs were enzymes. A group of EHPs (17.6%) were predicted as virulence factors. Proteins present in the pathogen but absent in the host were identified using host non-homology analysis. Further druggability analysis examined the druggable property of the proteins. Of 34, 27 essential pathogen-specific proteins which could serve as potential novel drug and vaccine targets. Druggability analysis was performed to examined the druggable property of the proteins. One target was found to be druggable and others were novel targets. The study's findings might assist in the development of new drugs for the treatment of Acinetobacter baumannii infections.