Application of pan genomics towards the druggability of Clostridium botulinum

Clostridium botulinum is Gram-positive anaerobic spore-forming bacterium that produces very potent neurotoxins that have a potential to be used as bioweapon. In this study, we utilized applications of pan genome to develop drug targets for 51 strains of Clostridium botulinum. From the total 8756 core proteins, there were 422 non-host homologous proteins from which we selected 7 essential proteins by applying 2 thresholds that are identity > 35 and e-value = 0.001. These 7 proteins were selected as drug targets and docked against 105 anti-bacterial compounds. After docking, against each protein, top 10 compounds were selected based on the binding affinity and number of interactions and from these 10 compounds, the most promising compound was ranked on top for all target proteins. Furthermore, we also identified some compounds that have shown highest binding energies with more than one protein. From the 105 anti-bacterial compounds, we got 39 compounds on the basis of their binding energies with all target proteins. These compounds can be further validated by in vitro analysis and can proceed for clinical trials.

Automated summary

This study utilized the pan genome to develop drug targets for 51 strains of Clostridium botulinum, selecting 7 essential proteins and docking them against 105 antibacterial compounds. The top 10 compounds with the highest binding affinity and number of interactions were chosen, with 39 promising compounds identified for further validation and clinical trials.