Goodman Andrew L, Kulasekara Bridget, Rietsch Arne, Boyd Dana, Smith Roger S, Lory Stephen
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Dev Cell. 2004 Nov;7(5):745-54. doi: 10.1016/j.devcel.2004.08.020.
The opportunistic pathogen Pseudomonas aeruginosa causes a variety of acute and chronic infections. We identified a gene whose inactivation results in attenuation of virulence due to premature activation of genes involved in biofilm formation and coordinate repression of genes required for initial colonization. This gene, retS, encodes a hybrid sensor kinase/response regulator with an unconventional arrangement of functional domains. Genome-wide transcriptional profiling indicates that the retS gene is required for expression of the Type III secretion system and other virulence factors and for repression of genes responsible for exopolysaccharide components of the P. aeruginosa biofilm matrix. These disparate phenotypes are suppressed by transposon insertions in genes encoding the GacS/GacA/rsmZ signal transduction pathway, a highly conserved system involved in the control of diverse adaptive functions. This study defines RetS as a pleiotropic regulator of multiple virulence phenotypes that orchestrates genes required for acute infection and genes associated with chronic persistence.
机会致病菌铜绿假单胞菌可引发多种急慢性感染。我们鉴定出一个基因，其失活会因生物膜形成相关基因的过早激活以及初始定植所需基因的协同抑制而导致毒力减弱。这个基因retS编码一种具有非常规功能域排列的杂合传感器激酶/反应调节因子。全基因组转录谱分析表明，retS基因对于III型分泌系统和其他毒力因子的表达以及对铜绿假单胞菌生物膜基质胞外多糖成分相关基因的抑制是必需的。这些不同的表型被编码GacS/GacA/rsmZ信号转导途径的基因中的转座子插入所抑制，该信号转导途径是一个高度保守的系统，参与多种适应性功能的控制。这项研究将RetS定义为多种毒力表型的多效调节因子，它协调急性感染所需的基因和与慢性持续存在相关的基因。
