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The Wolbachia endosymbiont as an anti-filarial nematode target.

Slatko, Barton E., Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 and Foster, Jeremy M. (2010) 'The Wolbachia endosymbiont as an anti-filarial nematode target.'. Symbiosis (Philadelphia, Pa.), Vol 51, Issue 1, pp. 55-65.

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Abstract

Human disease caused by parasitic filarial nematodes is a major cause of global morbidity. The parasites are transmitted by arthropod intermediate hosts and are responsible for lymphatic filariasis (elephantiasis) or onchocerciasis (river blindness). Within these filarial parasites are intracellular alpha-proteobacteria, Wolbachia, that were first observed almost 30 years ago. The obligate endosymbiont has been recognized as a target for anti-filarial nematode chemotherapy as evidenced by the loss of worm fertility and viability upon antibiotic treatment in an extensive series of human trials. While current treatments with doxycycline and rifampicin are not practical for widespread use due to the length of required treatments and contraindications, anti-Wolbachia targeting nevertheless appears a promising alternative for filariasis control in situations where current programmatic strategies fail or are unable to be delivered and it provides a superior efficacy for individual therapy. The mechanisms that underlie the symbiotic relationship between Wolbachia and its nematode hosts remain elusive. Comparative genomics, bioinfomatic and experimental analyses have identified a number of potential interactions, which may be drug targets. One candidate is de novo heme biosynthesis, due to its absence in the genome sequence of the host nematode, Brugia malayi, but presence in Wolbachia and its potential roles in worm biology. We describe this and several additional candidate targets, as well as our approaches for understanding the nature of the host-symbiont relationship.

Item Type: Article
Additional Information: The original publication is available at www.springerlink.com: http://www.springerlink.com/content/j841u42ln6901v54/ The article is also available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918796/?tool=pubmed
Uncontrolled Keywords: Symbiosis, Wolbachia, Brugia malayi, Filaria, Mutualism, Drug target
Subjects: QV Pharmacology > QV 34 Experimental pharmacology (General)
QX Parasitology > Helminths. Annelida > QX 203 Nematoda
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis
Digital Object Identifer (DOI): https://doi.org/10.1007/s13199-010-0067-1
Related URLs:
Depositing User: Mary Creegan
Date Deposited: 29 Oct 2010 09:16
Last Modified: 24 Jan 2022 15:38
URI: https://archive.lstmed.ac.uk/id/eprint/1645

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