Anthrax is a major
zoonotic disease of wildlife, and in places like West Africa, it can be caused by Bacillus anthracis in arid nonsylvatic savannahs, and by B. cereus biovar anthracis (Bcbva) in sylvatic rainforests. Bcbva-caused
anthrax has been implicated in as much as 38% of mortality in rainforest ecosystems, where insects can enhance the transmission of
anthrax-causing bacteria. While
anthrax is well-characterized in mammals, its transmission by insects points to an unidentified
anthrax-resistance mechanism in its vectors. In mammals, a secreted
anthrax toxin component, 83 kDa Protective
Antigen (PA83), binds to
cell-surface receptors and is cleaved by
furin into an evolutionary-conserved PA20 and a pore-forming PA63 subunits. We show that PA20 increases the resistance of Drosophila flies and Culex mosquitoes to bacterial challenges, without directly affecting the bacterial growth. We further show that the PA83 loop known to be cleaved by
furin to release PA20 from PA63 is, in part, responsible for the PA20-mediated protection. We found that PA20 binds directly to the Toll activating
peptidoglycan-recognition protein-SA (PGRP-SA) and that the Toll/NF-κB pathway is necessary for the PA20-mediated protection of infected flies. This effect of PA20 on innate immunity may also exist in mammals: we show that PA20 binds to human PGRP-SA ortholog. Moreover, the constitutive activity of Imd/NF-κB pathway in
MAPKK Dsor1 mutant flies is sufficient to confer the protection from
bacterial infections in a manner that is independent of PA20 treatment. Lastly, Clostridium septicum alpha toxin protects flies from
anthrax-causing bacteria, showing that other pathogens may help insects resist
anthrax. The mechanism of
anthrax resistance in insects has direct implications on insect-mediated
anthrax transmission for wildlife management, and with potential for applications, such as reducing the sensitivity of pollinating insects to bacterial pathogens.