Yorgey P, Rahme L G, Tan M W, Ausubel F M
Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Mol Microbiol. 2001 Sep;41(5):1063-76. doi: 10.1046/j.1365-2958.2001.02580.x.
We are exploiting the broad host range of the human opportunistic pathogen Pseudomonas aeruginosa strain PA14 to elucidate the molecular basis of bacterial virulence in plants, nematodes, insects and mice. In this report, we characterize the role that two PA14 gene products, MucD and AlgD, play in virulence. MucD is orthologous to the Escherichia coli periplasmic protease and chaperone DegP. DegP homologues are known virulence factors that play a protective role in stress responses in various species. AlgD is an enzyme involved in the biosynthesis of the exopolysaccharide alginate, which is hyperinduced in mucD mutants. A PA14 mucD mutant was significantly impaired in its ability to cause disease in Arabidopsis thaliana and mice and to kill the nematode Caenorhabditis elegans. Moreover, MucD was found to be required for the production of an extracellular toxin involved in C. elegans killing. In contrast, a PA14 algD mutant was not impaired in virulence in plants, nematodes or mice. A mucDalgD double mutant had the same phenotype as the mucD single mutant in the plant and nematode pathogenesis models. However, the mucDalgD double mutant was synergistically reduced in virulence in mice, suggesting that alginate can partially compensate for the loss of MucD function in mouse pathogenesis.
我们正在利用人类机会致病菌铜绿假单胞菌PA14广泛的宿主范围,来阐明细菌在植物、线虫、昆虫和小鼠中致病的分子基础。在本报告中,我们描述了PA14的两个基因产物MucD和AlgD在致病过程中所起的作用。MucD与大肠杆菌周质蛋白酶及伴侣蛋白DegP是直系同源物。DegP同源物是已知的致病因子,在多种物种的应激反应中发挥保护作用。AlgD是一种参与胞外多糖藻酸盐生物合成的酶,在mucD突变体中其表达被高度诱导。PA14的mucD突变体在引起拟南芥和小鼠发病以及杀死线虫秀丽隐杆线虫的能力上显著受损。此外,发现MucD是产生一种参与杀死秀丽隐杆线虫的细胞外毒素所必需的。相比之下,PA14的algD突变体在植物、线虫或小鼠中的致病力并未受损。在植物和线虫致病模型中,mucDalgD双突变体与mucD单突变体具有相同的表型。然而,mucDalgD双突变体在小鼠中的致病力协同降低,这表明藻酸盐可以部分补偿MucD功能在小鼠致病过程中的丧失。