Tan M W, Rahme L G, Sternberg J A, Tompkins R G, Ausubel F M
Department of Genetics, Harvard Medical School and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2408-13. doi: 10.1073/pnas.96.5.2408.
We reported recently that the human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills Caenorhabditis elegans and that many P. aeruginosa virulence factors (genes) required for maximum virulence in mouse pathogenicity are also required for maximum killing of C. elegans. Here we report that among eight P. aeruginosa PA14 TnphoA mutants isolated that exhibited reduced killing of C. elegans, at least five also exhibited reduced virulence in mice. Three of the TnphoA mutants corresponded to the known virulence-related genes lasR, gacA, and lemA. Three of the mutants corresponded to known genes (aefA from Escherichia coli, pstP from Azotobacter vinelandii, and mtrR from Neisseria gonorrhoeae) that had not been shown previously to play a role in pathogenesis, and two of the mutants contained TnphoA inserted into novel sequences. These data indicate that the killing of C. elegans by P. aeruginosa can be exploited to identify novel P. aeruginosa virulence factors important for mammalian pathogenesis.
我们最近报道，人类机会致病菌铜绿假单胞菌PA14菌株可杀死秀丽隐杆线虫，并且在小鼠致病性中发挥最大毒力所需的许多铜绿假单胞菌毒力因子（基因），在对秀丽隐杆线虫的最大杀伤中也是必需的。在此我们报道，在分离出的8株对秀丽隐杆线虫杀伤能力降低的铜绿假单胞菌PA14 TnphoA突变体中，至少有5株在小鼠中的毒力也降低。其中3个TnphoA突变体对应已知的毒力相关基因lasR、gacA和lemA。另外3个突变体对应已知基因（来自大肠杆菌的aefA、来自棕色固氮菌的pstP和来自淋病奈瑟菌的mtrR），这些基因以前未被证明在发病机制中起作用，还有2个突变体的TnphoA插入了新序列。这些数据表明，利用铜绿假单胞菌对秀丽隐杆线虫的杀伤作用，可鉴定出对哺乳动物发病机制重要的新型铜绿假单胞菌毒力因子。
