Core Proteome Subtractive Genomics Reveals Potential Therapeutic Targets in Bacillus anthracis

Bacillus anthracis, a Gram-positive, spore-forming bacterium, poses significant public health risks due to its zoonotic potential and historical use in bioterrorism. Pathogenicity of B. anthracis is primarily attributed to its genetic components, including the essential plasmids pXO1 and pXO2. The pXO1 plasmid encodes toxic factors, while pXO2 facilitates immune evasion. The zoonotic potential, as well as potential bio-threat, necessitates investigation into novel therapeutic targets. Through metabolic network analysis, docking, and notably subtractive genomics, researchers have effectively pinpointed pathogen-specific target proteins essential for drug development. Subtractive genomics, in particular, stands out for its cost-effectiveness and ability to identify non-host homologous targets. In this study, we used a core proteome immunoinformatic approach to identify potential therapeutic targets in B. anthracis. A total of 3987 proteins were found to be conserved in B. anthracis and among them, 388 were essential, non-human homologous proteins. These proteins were then subjected to localization and pathway analysis which resulted in 79 unique pathway proteins. Through PPI and druggability analysis, we had identified 17 strain-independent therapeutic target proteins. All the identified proteins are non-homologous to human proteins and, therefore, are potential targets for drug development. These potential target proteins are involved primarily in cell division, peptidoglycan biosynthesis, and putative flagellar assembly, which are essential for bacterial survival and pathogenicity. These identified target proteins could be the foundation for the development of therapeutics against human anthrax.