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

Quek, Shannon ORCID: https://orcid.org/0000-0002-1583-9541, Cook, Darren, Wu, Yang, Marriott, Amy, Steven, Andrew, Johnston, Kelly, Ford, Louise, Archer, John, Hemingway, Janet ORCID: https://orcid.org/0000-0002-3200-7173, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192, Wagstaff, Simon ORCID: https://orcid.org/0000-0003-0577-5537, Turner, Joseph ORCID: https://orcid.org/0000-0002-2185-5476 and Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 (2022) 'Wolbachia depletion blocks transmission of lymphatic filariasis by preventing chitinase-dependent parasite exsheathment'. Proceedings of the National Academy of Sciences, Vol 119, Issue 15, e2120003119.

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Abstract

Lymphatic filariasis is a vector-borne neglected tropical disease prioritized for global elimination. The filarial nematodes that cause the disease host a symbiotic bacterium, Wolbachia, which has been targeted using antibiotics, leading to cessation of parasite embryogenesis, waning of circulating larvae (microfilariae [mf]), and gradual cure of adult infection. One of the benefits of the anti-Wolbachia mode of action is that it avoids the rapid killing of mf, which can drive inflammatory adverse events. However, mf depleted of Wolbachia persist for several months in circulation, and thus patients treated with antibiotics are assumed to remain at risk for transmitting infections. Here, we show that Wolbachia-depleted mf rapidly lose the capacity to develop in the mosquito vector through a defect in exsheathment and inability to migrate through the gut wall. Transcriptomic and Western blotting analyses demonstrate that chitinase, an enzyme essential for mf exsheathment, is down-regulated in Wolbachia-depleted mf and correlates with their inability to exsheath and escape the mosquito midgut. Supplementation of in vitro cultures of Wolbachia-depleted mf with chitinase enzymes restores their ability to exsheath to a similar level to that observed in untreated mf. Our findings elucidate a mechanism of rapid transmission-blocking activity of filariasis after depletion of Wolbachia and adds to the broad range of biological processes of filarial nematodes that are dependent on Wolbachia symbiosis.

Item Type: Article
Subjects: QW Microbiology and Immunology > Bacteria > QW 150 Proteobacteria. Rickettsiaceae, Wolbachia
QX Parasitology > QX 20 Research (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1073/pnas.2120003119
Depositing User: Cathy Waldron
Date Deposited: 04 May 2022 11:10
Last Modified: 04 May 2022 11:10
URI: https://archive.lstmed.ac.uk/id/eprint/20224

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