A neurotoxin that specifically targets Anopheles mosquitoes

Estefania Contreras; Geoffrey Masuyer; Nadia Qureshi; Swati Chawla; Harpal S. Dhillon; Han Lim Lee; Jianwu Chen; Pål Stenmark; Sarjeet S. Gill

doi:10.1038/s41467-019-10732-w

A neurotoxin that specifically targets Anopheles mosquitoes

Estefania Contreras, Geoffrey Masuyer, Nadia Qureshi, Swati Chawla, Harpal S. Dhillon, Han Lim Lee, Jianwu Chen, Pål Stenmark, Sarjeet S. Gill

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

52 Citations (SciVal)

Abstract

Clostridial neurotoxins, including tetanus and botulinum neurotoxins, generally target vertebrates. We show here that this family of toxins has a much broader host spectrum, by identifying PMP1, a clostridial-like neurotoxin that selectively targets anopheline mosquitoes. Isolation of PMP1 from Paraclostridium bifermentans strains collected in anopheline endemic areas on two continents indicates it is widely distributed. The toxin likely evolved from an ancestral form that targets the nervous system of similar organisms, using a common mechanism that disrupts SNARE-mediated exocytosis. It cleaves the mosquito syntaxin and employs a unique receptor recognition strategy. Our research has an important impact on the study of the evolution of clostridial neurotoxins and provides the basis for the use of P. bifermentans strains and PMP1 as innovative, environmentally friendly approaches to reduce malaria through anopheline control.

Original language	English
Article number	2869
Pages (from-to)	1-10
Number of pages	10
Journal	Nature Communications
Volume	10
Issue number	1
Early online date	28 Jun 2019
DOIs	https://doi.org/10.1038/s41467-019-10732-w
Publication status	Published - 28 Jun 2019

Funding

We thank S. Pan from the University of California Proteomic Facility for his support in mass spectrometry analysis (supported by a NIH shared instrumentation grant (S10 OD010669)) and scientists at station ID30B of ESRF (Grenoble, France) for their support during crystallography data collection. We thank Dr. Daniel Lundin for help with the phylogenetic network. The research was funded in part through grants from the National Institutes of Health, 1 R01AI123390 and 1R21AI070873, and the University of California Agricultural Experiment Station CA-R-NEU-7395-H to S.S.G. and by the Swedish Research Council (2014–5667) and the Swedish Cancer Society to P.S.

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-019-10732-wLicence: CC BY

Cite this

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AU - Lee, Han Lim

AU - Chen, Jianwu

AU - Stenmark, Pål

AU - Gill, Sarjeet S.

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A neurotoxin that specifically targets Anopheles mosquitoes

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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