Anthrax toxin component, Protective Antigen, protects insects from bacterial infections

Area of Science:

• * Infectious Diseases
• * Insect Immunology
• * Molecular Biology

Background:

• * Anthrax, a zoonotic disease, affects wildlife globally, with Bacillus anthracis and B. cereus biovar anthracis causing significant mortality in different ecosystems.
• * Insects can transmit anthrax bacteria, yet the mechanisms of insect resistance to these pathogens remain largely unknown.
• * Mammalian anthrax toxin Protective Antigen (PA83) is cleaved into PA20 and PA63; PA20's role in insect immunity is unexplored.

Purpose of the Study:

• * To investigate the role of anthrax toxin component PA20 in insect resistance to bacterial infections.
• * To elucidate the molecular mechanisms underlying PA20-mediated protection in insects.
• * To explore potential parallels between insect and mammalian innate immune responses to anthrax.

Main Methods:

• * Administered PA20 to Drosophila flies and Culex mosquitoes and assessed their survival against bacterial challenges.
• * Investigated the interaction between PA20 and insect immune pathways, including Toll and Imd/NF-κB.
• * Examined the binding of PA20 to peptidoglycan-recognition protein-SA (PGRP-SA) and its human ortholog.

Main Results:

• * PA20 significantly increased the resistance of flies and mosquitoes to bacterial infections without affecting bacterial growth.
• * PA20 binds directly to insect PGRP-SA, activating the Toll/NF-κB pathway, which is crucial for protection.
• * PA20 also binds to human PGRP-SA, suggesting a conserved mechanism; other toxins like Clostridium septicum alpha toxin also confer protection.

Conclusions:

• * Anthrax toxin component PA20 confers innate immunity in insects by interacting with PGRP-SA and activating the Toll pathway.
• * The findings reveal a novel mechanism of insect resistance to bacterial pathogens with implications for disease transmission.
• * Understanding insect immunity to anthrax can inform wildlife management strategies and potential applications in protecting beneficial insects.