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Corallopyronin A Specifically Targets and Depletes Essential Obligate Wolbachia Endobacteria From Filarial Nematodes In Vivo

Schiefer, A., Schmitz, A., Schaberle, T. F., Specht, S., Lammer, C., Johnston, Kelly, Vassylyev, D. G., Konig, G. M., Hoerauf, A. and Pfarr, K. (2012) 'Corallopyronin A Specifically Targets and Depletes Essential Obligate Wolbachia Endobacteria From Filarial Nematodes In Vivo'. Journal of Infectious Diseases, Vol 206, Issue 2, pp. 249-257.

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Abstract

Doxycycline and rifampicin deplete essential Wolbachia from filarial nematodes that cause lymphatic filariasis or onchocerciasis, resulting in blocked worm development and death. However, doxycycline is contraindicated for children and pregnant/breastfeeding women, as is rifampicin in the latter group with the additional specter of possible resistance development in Mycobacterium spp. Novel antibiotics with a narrower spectrum would aid in eliminating filarial diseases. Corallococcus coralloides synthesizes corallopyronin A, a noncompetitive inhibitor of RNA polymerase ineffective against Mycobacterium spp. Corallopyronin A depleted Wolbachia from infected insect cells (1.89 Thus the antibiotic is effective against intracellular bacteria despite the many intervening surfaces (blood vessels, pleura, worm cuticle) and membranes (worm cell, vesicle, Wolbachia inner and outer membranes). Corallopyronin A is an antibiotic to develop further for filariasis elimination without concern for cross-resistance development in tuberculosis.

Item Type: Article
Subjects: QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified.
QX Parasitology > Helminths. Annelida > QX 301 Filarioidea
WB Practice of Medicine > Therapeutics > WB 330 Drug therapy
WC Communicable Diseases > Infection. Bacterial Infections > Other Bacterial Infections. Zoonotic Bacterial Infections > WC 302 Actinomycetales infections. Mycobacterium infections
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 885 Onchocerciasis
WF Respiratory System > Tuberculosis > WF 360 Drug therapy
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1093/infdis/jis341
Depositing User: Martin Chapman
Date Deposited: 18 Dec 2014 14:59
Last Modified: 06 Feb 2018 13:08
URI: http://archive.lstmed.ac.uk/id/eprint/4682

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