Delftia tsuruhatensis TC1 symbiont suppresses malaria transmission by anopheline mosquitoes

Author:

Huang Wei1ORCID,Rodrigues Janneth2ORCID,Bilgo Etienne3ORCID,Tormo José R.4ORCID,Challenger Joseph D.5ORCID,De Cozar-Gallardo Cristina2,Pérez-Victoria Ignacio4ORCID,Reyes Fernando4ORCID,Castañeda-Casado Pablo6ORCID,Gnambani Edounou Jacques3,Hien Domonbabele François de Sales3,Konkobo Maurice3,Urones Beatriz2,Coppens Isabelle1,Mendoza-Losana Alfonso2ORCID,Ballell Lluís2ORCID,Diabate Abdoulaye3ORCID,Churcher Thomas S.5ORCID,Jacobs-Lorena Marcelo1ORCID

Affiliation:

1. Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.

2. Global Health Medicines R&D, GSK, Tres Cantos, 28760 Madrid, Spain.

3. Institut de Recherche en Sciences de la Santé (IRSS), Bobo-Dioulasso BP: 545, Burkina Faso.

4. Fundación MEDINA, 18016 Armilla, Granada, Spain.

5. MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London W2 1PG, UK.

6. Drug Metabolism and Pharmacokinetics (DMPK) Discovery, In Vitro/In Vivo Translation (IVIVT), GSK, 28760 Tres Cantos, Madrid, Spain.

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 small-molecule 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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