Anti-filarial activity of antibiotic therapy is due to extensive apoptosis after Wolbachia depletion from filarial nematodes.

Landmann, Frederic, Voronin, Denis, Sullivan, William and Taylor, Mark ORCID: https://orcid.org/0000-0003-3396-9275 (2011) 'Anti-filarial activity of antibiotic therapy is due to extensive apoptosis after Wolbachia depletion from filarial nematodes.'. PLoS Pathogens, Vol 7, Issue 11, e1002351.

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Abstract

Filarial nematodes maintain a mutualistic relationship with the endosymbiont Wolbachia. Depletion of Wolbachia produces profound defects in nematode development, fertility and viability and thus has great promise as a novel approach for treating filarial diseases. However, little is known concerning the basis for this mutualistic relationship. Here we demonstrate using whole mount confocal microscopy that an immediate response to Wolbachia depletion is extensive apoptosis in the adult germline, and in the somatic cells of the embryos, microfilariae and fourth-stage larvae (L4). Surprisingly, apoptosis occurs in the majority of embryonic cells that had not been infected prior to antibiotic treatment. In addition, no apoptosis occurs in the hypodermal chords, which are populated with large numbers of Wolbachia, although disruption of the hypodermal cytoskeleton occurs following their depletion. Thus, the induction of apoptosis upon Wolbachia depletion is non-cell autonomous and suggests the involvement of factors originating from Wolbachia in the hypodermal chords. The pattern of apoptosis correlates closely with the nematode tissues and processes initially perturbed following depletion of Wolbachia, embryogenesis and long-term sterilization, which are sustained for several months until the premature death of the adult worms. Our observations provide a cellular mechanism to account for the sustained reductions in microfilarial loads and interruption of transmission that occurs prior to macrofilaricidal activity following antibiotic therapy of filarial nematodes.

Item Type:	Article
Subjects:	QU Biochemistry > Cells and Genetics > QU 375 Cell physiology QW Microbiology and Immunology > Bacteria > QW 150 Proteobacteria. Rickettsiaceae, Wolbachia QW Microbiology and Immunology > QW 52 Physiology and chemistry of microorganisms. Metabolism. QX Parasitology > Helminths. Annelida > QX 301 Filarioidea WC Communicable Diseases > Tropical and Parasitic Diseases > WC 770 Therapy 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/10.1371/journal.ppat.1002351
Depositing User:	Mary Creegan
Date Deposited:	05 Mar 2013 15:17
Last Modified:	16 Sep 2019 09:01
URI:	https://archive.lstmed.ac.uk/id/eprint/3233

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