Juhas Mario, Wiehlmann Lutz, Huber Birgit, Jordan Doris, Lauber Joerg, Salunkhe Prabhakar, Limpert Anna Silke, von Götz Franz, Steinmetz Ivo, Eberl Leo, Tümmler Burkhard
Clinical Research Group, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Department of Microbiology, Technical University Munich, Am Hochanger 4, D-85350 Freising, Germany.
Microbiology (Reading). 2004 Apr;150(Pt 4):831-841. doi: 10.1099/mic.0.26906-0.
Pathogenesis of Pseudomonas aeruginosa is controlled to a major extent by the two quorum-sensing systems las and rhl. The previously uncharacterized gene PA2591 was identified as a major virulence regulator, vqsR, in the quorum-sensing hierarchy. vqsR is a member of the LuxR family and possesses a las box in its upstream region. Transposon inactivation of vqsR abrogated the production of N-acylhomoserine lactones and the secretion of exoproducts and diminished bacterial virulence for Caenorhabditis elegans. Cytotoxicity towards macrophages was not affected. vqsR mRNA was expressed more strongly in the presence of human serum and oxidative stress than under standard growth conditions. High-density oligonucleotide microarrays were used to compare the global expression profile of a wild-type strain and a vqsR mutant. One-hundred-and-fifty-one and 113 genes were significantly differentially expressed in the presence of H(2)O(2) and human serum, respectively. The disruption of vqsR repressed the expression of genes that are known to be promoted by quorum sensing and activated the expression of genes that are known to be repressed by quorum sensing. Moreover, the vqsR mutant harboured less mRNA transcript for the production of siderophores and membrane-bound elements of antibiotic resistance. The protein encoded by PA2591 regulates several traits of pathogenicity; hence, the name vqsR ('virulence and quorum-sensing regulator') was assigned to PA2591.
铜绿假单胞菌的发病机制在很大程度上受群体感应系统las和rhl的控制。先前未被鉴定的基因PA2591被确定为群体感应层级中的主要毒力调节因子vqsR。vqsR是LuxR家族的成员，在其上游区域有一个las框。vqsR的转座子失活消除了N-酰基高丝氨酸内酯的产生和外产物的分泌，并降低了对秀丽隐杆线虫的细菌毒力。对巨噬细胞的细胞毒性不受影响。与标准生长条件相比，vqsR mRNA在人血清和氧化应激存在下表达更强。使用高密度寡核苷酸微阵列比较野生型菌株和vqsR突变体的全局表达谱。在H(2)O(2)和人血清存在下，分别有151个和113个基因显著差异表达。vqsR的破坏抑制了已知由群体感应促进的基因的表达，并激活了已知被群体感应抑制的基因的表达。此外，vqsR突变体中参与铁载体产生和抗生素抗性膜结合元件的mRNA转录本较少。由PA2591编码的蛋白质调节致病性的几个特征；因此，PA2591被命名为vqsR（“毒力和群体感应调节因子”）。
