title: Burkholderia pseudomallei suppresses Caenorhabditis elegans immunity by specific degradation of a GATA transcription factor.
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.
authors: School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia.
authors: Song-Hua
authors: SH
authors: Lee
authors: Rui-Rui
authors: RR
authors: Wong
authors: Chui-Yoke
authors: CY
authors: Chin
authors: Tian-Yeh
authors: TY
authors: Lim
authors: Su-Anne
authors: SA
authors: Eng
authors: Cin
authors: C
authors: Kong
authors: Nur Afifah
authors: NA
authors: Ijap
authors: Ming-Seong
authors: MS
authors: Lau
authors: Mei-Perng
authors: MP
authors: Lim
authors: Yunn-Hwen
authors: YH
authors: Gan
authors: Fang-Lian
authors: FL
authors: He
authors: Man-Wah
authors: MW
authors: Tan
authors: Sheila
authors: S
authors: Nathan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000276:immunology; D012323:RNA Processing, Post-Transcriptional; D018510:RNA, Helminth / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014774:Virulence / Q000276:immunology
chemical_list: D029742:Caenorhabditis elegans Proteins; C094134:ELT-2 protein, C elegans; D050980:GATA Transcription Factors; D018510:RNA, Helminth; D044767:Ubiquitin-Protein Ligases
keywords: innate immunity; ubiquitin–proteosomal system
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