Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor

Song Hua Lee, Rui Rui Wong, Chui Yoke Chin, Tian Yeh Lim, Su Anne Eng, Cin Kong, Nur Afifah Ijap, Ming Seong Lau, Mei Perng Lim, Yunn Hwen Gan, Fang Lian He, Man Wah Tan, Sheila Nathan

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin - proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.

Original languageEnglish
Pages (from-to)15067-15072
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number37
DOIs
Publication statusPublished - 10 Sep 2013

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GATA Transcription Factors
Burkholderia pseudomallei
Caenorhabditis elegans
Immunity
Burkholderia Infections
Proteasome Endopeptidase Complex
Ubiquitin
Gram-Negative Bacteria
Transcriptome
Genes
Virulence
Transcription Factors
Soil
Down-Regulation
Cell Culture Techniques
Genome
Infection
Proteins

Keywords

  • Innate immunity
  • Ubiquitin-proteosomal system

ASJC Scopus subject areas

  • General

Cite this

Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor. / Lee, Song Hua; Wong, Rui Rui; Chin, Chui Yoke; Lim, Tian Yeh; Eng, Su Anne; Kong, Cin; Ijap, Nur Afifah; Lau, Ming Seong; Lim, Mei Perng; Gan, Yunn Hwen; He, Fang Lian; Tan, Man Wah; Nathan, Sheila.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 37, 10.09.2013, p. 15067-15072.

Research output: Contribution to journalArticle

Lee, Song Hua ; Wong, Rui Rui ; Chin, Chui Yoke ; Lim, Tian Yeh ; Eng, Su Anne ; Kong, Cin ; Ijap, Nur Afifah ; Lau, Ming Seong ; Lim, Mei Perng ; Gan, Yunn Hwen ; He, Fang Lian ; Tan, Man Wah ; Nathan, Sheila. / Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 37. pp. 15067-15072.
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