Oza Javin P, Yeh Jimmy B, Reich Norbert O
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA.
FEMS Microbiol Lett. 2005 Apr 1;245(1):53-9. doi: 10.1016/j.femsle.2005.02.030.
Salmonella enterica serovar Typhimurium was previously shown to be virulent in Caenorhabditis elegans. Here we demonstrate that DNA adenine methyltransferase (DAM) modulates Salmonella virulence in the nematode, as it does in mice. After 5 days of continual exposure to bacteria, twice as many worms died when exposed to the wild-type than the dam-mutant strain of Salmonella. Similar trends in virulence were observed when worms were exposed to Salmonella strains for 5 h and transferred to the avirulent Escherichia coli OP50. While a 10-fold attenuation was observed in the absence of DAM, the dam-strain was still able to infect and persist in the host worm. Our results further support the use of C. elegans as an accessible and readily studied animal model of bacterial pathogenesis. However, our results suggest that crucial host responses differ between the murine and nematode models. Additionally, we carried out preliminary liquid culture based experiments with the long term goal of developing high throughput animal based screens of DAM inhibitors.
肠炎沙门氏菌鼠伤寒血清型先前已被证明对秀丽隐杆线虫具有致病性。在此我们证明,DNA腺嘌呤甲基转移酶(DAM)对线虫中沙门氏菌毒力的调节作用与在小鼠中一样。在持续接触细菌5天后,暴露于野生型沙门氏菌的线虫死亡数量是暴露于dam突变株的两倍。当线虫接触沙门氏菌菌株5小时后再转移到无毒的大肠杆菌OP50中时,也观察到了类似的毒力趋势。虽然在没有DAM的情况下观察到毒力降低了10倍,但dam菌株仍能够感染宿主线虫并在其中存活。我们的结果进一步支持将秀丽隐杆线虫用作研究细菌致病机制的易于获取且便于研究的动物模型。然而,我们的结果表明,小鼠模型和线虫模型中关键的宿主反应有所不同。此外,我们开展了基于液体培养的初步实验,其长期目标是开发基于动物的DAM抑制剂高通量筛选方法。