Effect of Wolbachia depletion on Brugia malayi development in A. aegypti mosquitoes

Lymphatic filariasis is a vector-borne Neglected Tropical Disease prioritised for global elimination. The filarial nematodes which cause the disease hosts a symbiotic bacterium, Wolbachia, which has been targeted using antibiotics, leading to cessation of parasite embryogenesis, waning of circulating larvae (microfilariae; mf) and gradual cure of adult infection. However, mf depleted of Wolbachia persist for several months in circulation and thus patients treated with antibiotics are assumed to remain at risk of transmitting infections. Using multiple laboratory techniques, including transcriptomics, we show that Wolbachia-depleted mf rapidly lose the capacity to develop in the mosquito vector via a defect in exsheathment, and inability to migrate through the gut wall. This transcriptomics experiment utilised three biological replicates of mf treated for six weeks with tetracycline or with matched untreated controls, resulting in over 90% depletion in mf development rate to the infective L3 stage.