Antiviral, antiparasitic, and cytotoxic effects of 5,6-dihydroxyindole, a reactive compound

Prophenoloxidase and its activation are involved in several defense responses of insects. Upon wounding or infection, inactive prophenoloxidase is converted to active phenoloxidase through a network of serine proteases and serine protease homologues. Phenoloxidase generates reactive compounds such as 5,6-dihydroxyindole (DHI), which possess a broad-spectrum antimicrobial activity [Zhao et al., 2007]. Here we demonstrate that DHI and its spontaneous oxidation products are active against viruses and parasitic wasp eggs. Over 97% of baculoviruses were killed after 3 h treatment with 1.25 mM DHI and the LC50 for ë bacteriophage was 5.61 ± 2.21 µM DHI, suggesting that prophenoloxidase activation is a component of the antiviral response in insects. Incubating eggs of the parasitic wasp Microplitis demolitor with DHI led to 50% fatality at 111.0 ± 1.6 µM, indicating that phenoloxidase-generated reactive intermediates participate in the host defense against incompatible parasitoids. The toxicity of DHI and related compounds is not limited to invading organisms (e.g., viruses, bacteria, fungi, and parasitoids): 50% of Spodoptera frugiperda Sf9 cells were killed by DHI at a concentration of 131.8 ± 1.1 µM. DHI caused DNA polymerization, protein crosslinking, and abnormal cytoskeleton remodeling, which might be responsible for its toxicity. These results suggest prophenoloxidase activation, if not properly controlled, could damage host tissues and cells as well. Therefore, regulatory mechanisms have to be in place to ensure this potent antibiotic activity is a local, transient response against nonself.