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

作者：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

来源：Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(37): 15067-15072.

DOI：10.1073/pnas.1311725110

• innate immunity
• ubiquitin-proteosomal system

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 similar to 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.

• 出版日期2013-9-10