In Silico Identification of Novel Drug Targets in the Honeybee Pathogen Paenibacillus larvae and Molecular Docking Studies

Paenibacillus larvae, a Gram-positive bacterium, is the pathogen responsible for American foulbrood (AFB), a prevalent disease that afflicts honeybees in numerous countries. P. larvae exclusively infect the honeybee larva, with no known environment supporting its germination or growth. In recent years, various methods, including fungicides, antibiotics, indoles, and bacteriophages, have been used to mitigate the harmful impact of P. larvae on honeybees. While these approaches offer therapeutic benefits, they also have drawbacks, such as antibiotic resistance and the adverse effects of these chemical compounds on hives, honey, and human health. This study presents a comprehensive method for identifying potential drug targets in P. larvae using a reverse vaccinology protocol. By using this approach, 11 putative drug targets in 9 different P. larvae subspecies were identified. Furthermore, this study provides a list of 7 potential inhibitors resulting from a thorough computational simulation of the interactions between these drug targets and bioactive compounds. In summary, this study suggests that the newly identified drug targets and their corresponding bioactive compounds may be invaluable in the development of therapeutic drugs for controlling P. larvae, the causative agent of AFB in honeybees.