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 | |
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