In vitro antibacterial activity of macelignan and corosolic acid against the bacterial bee pathogens Paenibacillus larvae and Melissocoecus plutonius

Foulbrood disease, which is caused by Paenibacillus larvae (American foulbrood) or Melissococcus plutonius (European foulbrood disease), is a major threat to honeybees (Apis mellifera) worldwide. Tetracycline derivatives have been used to control these bacteria, but resistant strains have evolved, and the antibiotic derivatives can adversely affect bee health. When foulbrood disease is discovered, beekeepers usually burn the bee hives and equipment. The aim of this study was to investigate the in vitro susceptibility of P. larvae and M. plutonius to new antibacterial agents. Antibacterial activities of seven compounds prepared as serial two-fold dilutions were assayed using 96-well microtitre plates. Minimum inhibitory concentration values were obtained after 24 h or 48 h of incubation. Antibacterial synergistic activity of tetracycline and the test compounds was evaluated using broth micro-dilution assays with two-fold serial dilutions of the compounds. Among the seven compounds tested, macelignan and corosolic acid showed the strongest anti-bacterial activity. In addition, tetracycline interacted synergistically with corosolic acid to reduce P. larvae and M. plutonius growth. Even though macelignan and corosolic acid were worth as solely effective agents to treat P. larvae and M. plutonius, combinatorial treatment with tetracycline would be more useful to overcome toxicity, resistance occurrence and costliness. Further validation studies of these compounds and identification of their targets, as well as actual field tests and bee toxicity studies are still needed. However, macelignan and corosolic acid as natural secondary metabolites would be effective agents for bee foulbrood disease with valuable antibacterial activities.