Wolbachia depletion blocks transmission of lymphatic filariasis by preventing chitinase-dependent parasite exsheathment

Author:

Quek Shannon1,Cook Darren A. N.1,Wu Yang1,Marriott Amy E.1,Steven Andrew1,Johnston Kelly L.1,Ford Louise1ORCID,Archer John1,Hemingway Janet2ORCID,Ward Stephen A.1,Wagstaff Simon C.1,Turner Joseph D.1ORCID,Taylor Mark J.1ORCID

Affiliation:

1. Centre for Neglected Tropical Diseases, Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom

2. Centre for Neglected Tropical Diseases, Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, United Kingdom

Abstract

Significance Lymphatic filariasis caused by Wuchereria bancrofti , Brugia malayi , and Brugia timori affects 51 million people, leading to severe physical and mental disabilities. A mutualistic symbiosis between these filarial nematodes and Wolbachia bacteria has been exploited as a new curative treatment. Epidemiological modeling of anti- Wolbachia treatment assumes that transmission persists due to the lag phase before microfilariae (mf) become removed from circulation. Here, we show that Wolbachia -depleted mf cannot develop within the mosquito vector—a phenotype associated with down-regulation of B. malayi mf-specific chitinase, an enzyme essential for exsheathment. Our findings add to the broad range of host biological processes dependent on Wolbachia and suggest that anti- Wolbachia treatment mediates a more accelerated impact on elimination of lymphatic filariasis than currently predicted.

Funder

Bill and Melinda Gates Foundation

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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