Computational Study for the Identification of Novel Therapeutic Targets in Haemophilus influenzae by Subtractive Genomics Approach

Introduction: Haemophilus influenzae, a gram-negative, facultative anaerobic coccobacillus, is a member of the Pasteurellaceae family. It causes a variety of invasive and non-invasive bacterial infections known as H. influenzae infections. The increasing prevalence of antibiotic resistance highlights the need to identify novel therapeutic targets for treating H. influenzae infections. The emerging trends in the field of Pharmacoinformatics have aided in the prediction of novel putative therapeutic targets. Objective: This study aims to identify novel putative therapeutic targets in H. influenzae using a subtractive genomic approach. Methods: Subtractive Genomics, a simple yet powerful approach for the identification of novel therapeutic targets for bacterial pathogens, was employed in this study. The core proteome of 72 strains of H. influenzae was analysed through a multi-step filtration process to exclude the non-essential proteins and those homologous to the human proteome. Metabolic pathway analysis was conducted to identify pathogen-specific proteins, followed by druggability analysis and three-dimensional structure prediction. Results and Discussion: On analysing the core proteome, 115 proteins were found to be unique and non-homologous to the human proteome. Further screening of these proteins led to the identification of 25 proteins involved in the 29 unique metabolic pathways of bacteria. Subsequent analysis finally resulted in the identification of five novel therapeutic targets for H. influenzae that are unique, non-homologous to the human proteome, essential for bacterial survival, and involved in unique metabolic pathways of bacteria. Conclusion: This study successfully identified five novel therapeutic targets through subtractive genomics, contributing to the efforts against antimicrobial resistance in H. influenzae. Further experimental validation is necessary to strengthen these findings and advance therapeutic development.