Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 206, Issue 2, Pages 249-257Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jis341
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Funding
- German Research Foundation [PF 673/3-1, KO 902/5-1]
- University Hospital Bonn (BONFOR)
- National Institutes of Health [GM074840]
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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 mu M vs 7.8 mu M of doxycycline). In vivo, corallopyronin A depleted Wolbachia by 4.7-logs, resulting in impeded worm development. 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.
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