Proteogenomic analysis of Serratia marcescens using computational subtractive genomics approach

Serratia marcescens, a Gram-negative bacterium (Enterobacteriaceae) is a hospital-acquired opportunistic pathogen that infects the urinary and central nervous systems. The identification of new therapeutics against S. marcescens is crucial since it is now multi-drug resistant. Therefore, the current study was aimed to identify potential drug targets against S. marcescens strains i.e. WW4, SM39, and Db11 using comparative metabolic pathway analysis and subtractive genomics approach. The applied bioinformatics-based method was used to identify the unique metabolic pathways as the prioritized drug targets. The downstream analysis has led to the identification of three pathways that are specifically absent and/or present in the specific strain. Consequently, six proteins were identified through subtractive genomic analysis. The identified proteins were found as non-homologous and essential to the pathogen's survival as well as unique to the WW4 strain. The estimated features proposed it as a potential drug target. The selected protein was further subjected to in-depth structural analysis for the structure modeling, structure validation, and protein-protein interaction analysis. Furthermore, the library of ~1500 approved compounds was screened against selected drug target to identify potential drug candidates. The current work may help in repurposing of the drug compounds as novel medication against S. marcescens.