Analysis of transcriptional regulation of tetracycline responsive genes in Brugia malayi

Canhui Liu, Patrick Vander Kelen, Elodie Ghedin, Sara Lustigman, Thomas R. Unnasch

Research output: Contribution to journalArticle

Abstract

The Wolbachia endosymbiont of the human filarial parasites is necessary for parasite reproduction, making it an attractive chemotherapeutic target. Previous studies have demonstrated that mRNA levels of several nuclearly encoded genes are altered as a result of exposure to antibiotics that eliminate the endosymbiont, suggesting that they may be involved in maintaining the parasite-endosymbiont relationship. Here, we tested the hypothesis that the increase in mRNA levels of certain nuclearly encoded genes of Brugia malayi in response to tetracycline treatment involved specific regulatory elements present in the promoters of these genes. The promoters of three such genes (BmRPL13, BmRPS4 and BmHSP70) were tested for tetracycline responsiveness utilizing a homologous transient transcription system. Reporter gene expression driven by all three promoters was up-regulated in transfected embryos exposed to tetracycline. Substitution mutagenesis was employed to map the cis-acting elements responsible for this response in the BmHSP70 promoter. Tetracycline responsiveness was found to be distinct from the cis-acting elements involved in regulating the stress response from the BmHSP70 promoter; rather, tetracycline responsiveness was mediated by a TATAA-box like element. This study represents the first demonstration of small molecule-mediated gene regulation of a native B. malayi promoter.

Original languageEnglish (US)
Pages (from-to)106-111
Number of pages6
JournalMolecular and Biochemical Parasitology
Volume180
Issue number2
DOIs
StatePublished - Dec 2011

Keywords

  • Filariasis
  • Promoter
  • Transfection
  • Wolbachia

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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