Effects of doxycycline on gene expression in Wolbachia and Brugia malayi adult female worms in vivo

Rao, Ramakrishna U and Huang, Yuefang and Abubucker, Sahar and Heinz, Michael and Crosby, Seth D. and Mitreva, Makedonka and Weil, Gary J. (2012) Effects of doxycycline on gene expression in Wolbachia and Brugia malayi adult female worms in vivo. Journal of Biomedical Science, 19 (21). pp. 1-15.

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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.

Item Type: Article
Uncontrolled Keywords: Doxycycline, Brugia malayi, Wolbachia, Filariasis, Gene expression, Microarray
Subjects: Medical and Health Sciences > Basic medicine
Divisions: Faculty of Medical Science
Depositing User: Mirjana Kocaleva
Date Deposited: 03 Dec 2012 11:52
Last Modified: 03 Dec 2012 11:52
URI: https://eprints.ugd.edu.mk/id/eprint/2900

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