Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes

Abstract

Malaria control demands the development of a wide range of complementary strategies. We describe the properties of a naturally occurring, non–genetically modified symbiotic bacterium, Delftia tsuruhatensis TC1, which was isolated from mosquitoes incapable of sustaining the development of Plasmodium falciparum parasites. D. tsuruhatensis TC1 inhibits early stages of Plasmodium development and subsequent transmission by the Anopheles mosquito through secretion of a smallmolecule inhibitor. We have identified this inhibitor to be the hydrophobic molecule harmane. We also found that, on mosquito contact, harmane penetrates the cuticle, inhibiting Plasmodium development. D. tsuruhatensis TC1 stably populates the mosquito gut, does not impose a fitness cost on the mosquito, and inhibits Plasmodium development for the mosquito’s life. Contained field studies in Burkina Faso and modeling showed that D. tsuruhatensis TC1 has the potential to complement mosquito-targeted malaria transmission control.GSK R&D supported and funded the work conducted at Johns Hopkins Bloomberg School of Public Health, Institut de Recherche en Sciences de la Santé (IRSS), and Fundación MEDINA. Funding from the Bill and Melinda Gates Foundation (Global Health Grant OPP1179809) and support from the Bloomberg Philanthropies is also acknowledged. A.D. and E.B. acknowledge funding from GSK under contract RDP-CW244389-IRSS-SA. J.D.C. and T.S.C. acknowledge funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), which is jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth and Development Office (FCDO), under the MRC/FCDO Concordat agreement, and is also part of the EDCTP2 program supported by the European Union.Peer reviewe