title: Corallopyronin A specifically targets and depletes essential obligate Wolbachia endobacteria from filarial nematodes in vivo.
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.
authors.affiliation: Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schiefer
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmitz
authors.forename: Till F
authors.initials: TF
authors.lastname: Schäberle
authors.forename: Sabine
authors.initials: S
authors.lastname: Specht
authors.forename: Christine
authors.initials: C
authors.lastname: Lämmer
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Johnston
authors.forename: Dmitry G
authors.initials: DG
authors.lastname: Vassylyev
authors.forename: Gabriele M
authors.initials: GM
authors.lastname: König
authors.forename: Achim
authors.initials: A
authors.lastname: Hoerauf
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pfarr
mesh_terms: D000330:Aedes / Q000166:cytology / Q000382:microbiology; D000818:Animals; D002460:Cell Line; D000075202:Contraindications; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005368:Filariasis / Q000188:drug therapy / Q000469:parasitology; D005369:Filaricides / Q000494:pharmacology; D005370:Filarioidea / Q000382:microbiology*; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008968:Molecular Conformation; D012293:Rifampin / Q000494:pharmacology; D013559:Symbiosis; D020577:Wolbachia / Q000187:drug effects* / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D005369:Filaricides; D007783:Lactones; C532894:corallopyronin A; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin