Transgenic Metarhizium Pingshaense Synergistically Ameliorates Pyrethroid-Resistance In Wild-Caught, Malaria-Vector Mosquitoes

Transgenic Metarhizium pingshaense expressing the spider neurotoxin Hybrid (Met-Hybrid) kill mosquitoes faster and at lower spore doses than wild-type strains. In this study, we demonstrate that this approach dovetails with the cornerstone of current malaria control: pyrethroid-insecticides, which are the cornerstone of current malaria control. We used World Health Organization (WHO) tubes, to compare the impact on insecticide resistance of Met-Hybrid with red fluorescent M. pingshaense (Met-RFP), used as a proxy for the wild-type fungus. Insecticides killed less than 20% of Anopheles coluzzii and Anopheles gambiae s.s. mosquitoes collected in a malaria endemic region of Burkina Faso where pyrethroid use is common. Seven days post-infection, mortality for insecticide-sensitive and resistant mosquitoes averaged 94% with Met-Hybrid and 64% with Met-RFP, with LT80 values of 5.32 +/- 0.199 days and 7.76 +/- 0.183 days, respectively. Eighty nine percent of insecticide-resistant mosquitoes exposed to permethrin five days post-infection with Met-Hybrid died within 24 hours: only 22% died from Met-Hybrid alone over this 24-hour period. Compared to MetRFP, Met-Hybrid also significantly reduced flight capacity of mosquitoes 3 to 5 days post-infection. Based on WHOPES phase I laboratory susceptibility bioassays, transgenic Met-Hybrid provides effective biological control for adult African malaria vectors that may be used to synergistically manage insecticide resistance with current methods.