brugia malayi gene expression in response to the targeting of the wolbachia endosymbiont by tetracycline treatment与象皮病马来应对目标基因表达的沃尔巴克氏体属内共生体的四环素治疗.pdf

Brugia malayi Gene Expression in Response to the Targeting of the Wolbachia Endosymbiont by Tetracycline Treatment 1 2 1 1 2 Elodie Ghedin *, Tiruneh Hailemariam , Jay V. DePasse , Xu Zhang , Yelena Oksov , Thomas R. Unnasch3, Sara Lustigman2 1 University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America, 2 Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America, 3 Department of Global Health, University of South Florida, Tampa, Florida, United States of America Abstract Background: Brugia malayi, like most human filarial parasite species, harbors an endosymbiotic bacterium of the genus Wolbachia. Elimination of the endosymbiont leads to sterilization of the adult female. Previous biochemical and genetic studies have established that communication with its endobacterium is essential for survival of the worm. Methodology/Principal findings: We used electron microscopy to examine the effects of antibiotic treatment on Wolbachia cell structure. We have also used microarray and quantitative RT-PCR analyses to examine the regulation of the B. malayi transcripts altered in response to the anti-Wolbachia treatment. Microscopy of worms taken from animals treated with tetracycline for 14 and 21 days (14 d and 21 d) demonstrated substantial morphologic effects on the Wolbachia endobacterium by 14 d and complete degeneration of the endobacterial structures by 21 d. We observed upregulation of transcripts primarily encoding proteins involved in amino acid synthesis and protein translation, and downregulation of transcripts involved in cuticle biosynthesis after both 7 d and 14 d of treatment. In worms exposed to