- 作者: Ramakrishna U Rao, Yuefang Huang, Sahar Abubucker, Michael Heinz, Seth D Crosby, Makedonka Mitreva and Gary J Weil
- 作者服務機構: Infectious Diseases Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America
- 中文摘要: --
- 英文摘要:
Background: Most filarial nematodes contain Wolbachia symbionts. The purpose of this study was to
examine the effects of doxycycline on gene expression in Wolbachia and adult female
Brugia malayi.
Methods: Brugia malayi infected gerbils were treated with doxycycline for 6-weeks. This treatment
largely cleared Wolbachia and arrested worm reproduction. RNA recovered from treated
and control female worms was labeled by random priming and hybridized to the Version
2- filarial microarray to obtain expression profiles.
Results and discussion: Results showed significant changes in expression for 200 Wolbachia (29% of Wolbachia
genes with expression signals in untreated worms) and 546 B. malayi array elements after
treatment. These elements correspond to known genes and also to novel genes with
unknown biological functions. Most differentially expressed Wolbachia genes were
down-regulated after treatment (98.5%). In contrast, doxycycline had a mixed effect on
B. malayi gene expression with many more genes being significantly up-regulated after
treatment (85% of differentially expressed genes). Genes and processes involved in
reproduction (gender-regulated genes, collagen, amino acid metabolism, ribosomal
processes, and cytoskeleton) were down-regulated after doxycycline while up-regulated
genes and pathways suggest adaptations for survival in response to stress (energy
metabolism, electron transport, anti-oxidants, nutrient transport, bacterial signaling
pathways, and immune evasion).
Conclusions
Doxycycline reduced Wolbachia and significantly decreased bacterial gene expression.
Wolbachia ribosomes are believed to be the primary biological target for doxycycline in
filarial worms. B. malayi genes essential for reproduction, growth and development were
also down-regulated; these changes are consistent with doxycycline effects on embryo
development and reproduction. On the other hand, many B. malayi genes involved in
energy production, electron-transport, metabolism, anti-oxidants, and others with
unknown functions had increased expression signals after doxycycline treatment. These
results suggest that female worms are able to compensate in part for the loss of
Wolbachia so that they can survive, albeit without reproductive capacity. This study of
doxycycline induced changes in gene expression has provided new clues regarding the
symbiotic relationship between Wolbachia and B. malayi. - 中文關鍵字: --
- 英文關鍵字: Doxycycline, Brugia malayi, Wolbachia, Filariasis, Gene expression, Microarray