< i > In vivo < /i > efficacy of the boron-pleuromutilin AN11251 against < i > Wolbachia < /i > of the rodent filarial nematode < i > Litomosoides sigmodontis < /i >

by Alexandra Ehrens, Christopher S. Lunde, Robert T. Jacobs, Dominique Struever, Marianne Koschel, Stefan J. Frohberger, Franziska Lenz, Martina Fendler, Joseph D. Turner, Stephen A. Ward, Mark J. Taylor, Yvonne R. Freund, Rianna Stefanakis, Eric Easom, Xianfeng Li, Jacob J. Plattner, Achim Hoerauf, Marc P. H übner The elimination of filarial diseases such as onchocerciasis and lymphatic filariasis is hampered by the lack of a macrofilaricidal–adult worm killing–drug. In the present study, we tested thein vivo efficacy of AN11251, a boron-pleuromutilin that targets endosymbioticWolbachia bacteria from filarial nematodes and compared its efficacy to doxycycline and rifampicin. Doxycycline and rifampicin were previously shown to depleteWolbachia endosymbionts leading to a permanent sterilization of the female adult filariae and adult worm death in human clinical studies. Twice-daily oral treatment ofLitomosoides sigmodontis-infected mice with 200 mg/kg AN11251 for 10 days achieved aWolbachia depletion> 99.9% in the adult worms, exceeding theWolbachia reduction by 10-day treatments with bioequivalent human doses of doxycycline and a similar reduction as high-dose rifampicin (35 mg/kg).Wolbachia reductions of> 99% were also accomplished by 14 days of oral AN11251 at a lower twice-daily dose (50 mg/kg) or once-per-day 200 mg/kg AN11251 treatments. The combinations tested of AN11251 with doxycycline had no clear beneficial impact onWolbachia depletion, achieving a> 97%Wolbach...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research