Functional assignment for essential hypothetical proteins of Staphylococcus aureus N315

Staphylococcus aureus, the causative agent of nosocomial infections worldwide, has acquired resistance to almost all antibiotics stressing the need to develop novel drugs against this pathogen. In S. aureus N315, 302 genes have been identified as essential genes, indispensable for growth and survival of the pathogen. The functions of 40 proteins encoded by S. aureus 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, whose performance was assessed by Receiver operating characteristic curve analysis. Evaluation of physicochemical parameters, homology search against known proteins, domain analysis, subcellular localization analysis and virulence prediction assisted us to characterize EHPs. Functional assignment for 35 EHPs was made with high confidence. They belong to different functional classes like enzymes, binding proteins, miscellaneous proteins, helicases, transporters and virulence factors. Around 35% of EHPs were from hydrolases family. A group of EHPs (32.5%) were predicted as virulence factors. Of 35, 19 essential pathogen-specific proteins were considered as probable drug targets. Two targets were found to be druggable and others were novel targets. Outcome of the study could aid to identify novel drugs for better treatment of S. aureus infections.