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Autophagy regulates Wolbachia populations across diverse symbiotic associations.

Voronin, Denis, Cook, Darren, Steven, Andrew and Taylor, Mark (2012) 'Autophagy regulates Wolbachia populations across diverse symbiotic associations.'. Proceedings of the National Academy of Sciences of the United States of America, Vol 109, Issue 25, E1638-E1646.

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Abstract

Wolbachia are widespread and abundant intracellular symbionts of arthropods and filarial nematodes. Their symbiotic relationships encompass obligate mutualism, commensalism, parasitism, and pathogenicity. A consequence of these diverse associations is that Wolbachia encounter a wide range of host cells and intracellular immune defense mechanisms of invertebrates, which they must evade to maintain their populations and spread to new hosts. Here we show that autophagy, a conserved intracellular defense mechanism and regulator of cell homeostasis, is a major immune recognition and regulatory process that determines the size of Wolbachia populations. The regulation of Wolbachia populations by autophagy occurs across all distinct symbiotic relationships and can be manipulated either chemically or genetically to modulate the Wolbachia population load. The recognition and activation of host autophagy is particularly apparent in rapidly replicating strains of Wolbachia found in somatic tissues of Drosophila and filarial nematodes. In filarial nematodes, which host a mutualistic association with Wolbachia, the use of antibiotics such as doxycycline to eliminate Wolbachia has emerged as a promising approach to their treatment and control. Here we show that the activation of host nematode autophagy reduces bacterial loads to the same magnitude as antibiotic therapy; thus we identify a bactericidal mode of action targeting Wolbachia that can be exploited for the development of chemotherapeutic agents against onchocerciasis, lymphatic filariasis, and heartworm.

Item Type: Article
Uncontrolled Keywords: Brugia malayi; innate immunity; chemotherapy; helminth; endosymbiont
Subjects: QX Parasitology > Helminths. Annelida > QX 203 Nematoda
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1073/pnas.1203519109
Depositing User: Mary Creegan
Date Deposited: 10 Aug 2012 10:59
Last Modified: 06 Feb 2018 13:04
URI: http://archive.lstmed.ac.uk/id/eprint/2870

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