Smith, D. F. Q.; Camacho, E.; Thakur, R.; Barron, A. J.; Dong, Y.; Dimopoulos, G.; Broderick, N. A.; Casadevall, A.

Melanin, a black-brown pigment found throughout all kingdoms of life, has diverse biological functions including: UV protection, thermoregulation, oxidant scavenging, arthropod immunity, and microbial virulence. Given melanins broad roles in the biosphere, particularly in insect immune defenses, it is important to understand how exposure to ubiquitous environmental contaminants affects melanization. Glyphosate - the most widely used herbicide globally - inhibits melanin production, which could have wide-ranging implications in the health of many organisms, including insects. Here, we demonstrate that glyphosate has deleterious effects on insect health in two evolutionary distant species, Galleria mellonella (Lepidoptera: Pyralidae) and Anopheles gambiae (Diptera: Culicidae), suggesting a broad effect in insects. Glyphosate reduced survival of G. mellonella caterpillars following infection with the fungus Cryptococcus neoformans and decreased the size of melanized nodules formed in hemolymph, which normally help eliminate infection. Glyphosate also increased the burden of the malaria- causing parasite Plasmodium falciparum in A. gambiae mosquitoes, altered uninfected mosquito survival, and perturbed the microbial composition of adult mosquito midguts. Our results show that glyphosates mechanism of melanin inhibition involves antioxidant synergy and disruption of the reaction oxidation-reduction balance Overall, these findings suggest that glyphosates environmental accumulation could render insects more susceptible to microbial pathogens due to melanin inhibition, immune impairment, and perturbations in microbiota composition, potentially contributing to declines in insect populations.