Wolfgang Matthew C, Jyot Jeevan, Goodman Andrew L, Ramphal Reuben, Lory Stephen
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6664-8. doi: 10.1073/pnas.0307553101. Epub 2004 Apr 14.
Cystic fibrosis (CF) patients are highly susceptible to chronic lung infections by the environmental bacterium Pseudomonas aeruginosa. The overproduction and accumulation of dehydrated viscous respiratory mucus and excessive inflammation represents a defining feature of CF and constitutes the major environment encountered by P. aeruginosa during chronic infections. We applied whole-genome microarray technology to investigate the ability of P. aeruginosa to respond to signals found in muco-purulent airway liquids collected from chronically infected CF patients. Particularly notable was the activation of the Rhl-dependent quorum-sensing (QS) network and repression of fliC, which encodes flagellin. Activation of the Rhl branch of the QS network supports the observation that QS molecules are produced in the chronically infected CF lung. The shut-off of flagellin synthesis in response to CF airway liquids was rapid and independent of QS and the known regulatory networks controlling the hierarchical expression of flagellar genes. As flagellin is highly immunogenic and subject to detection by host pattern recognition receptors, its repression may represent an adaptive response that allows P. aeruginosa to avoid detection by host defense mechanisms and phagocytosis during the chronic phase of CF lung infections.
囊性纤维化（CF）患者极易受到环境细菌铜绿假单胞菌的慢性肺部感染。脱水粘性呼吸道黏液的过度产生和积累以及过度炎症是CF的一个决定性特征，也是铜绿假单胞菌在慢性感染期间遇到的主要环境。我们应用全基因组微阵列技术来研究铜绿假单胞菌对从慢性感染的CF患者收集的黏液脓性气道液体中发现的信号作出反应的能力。特别值得注意的是Rhl依赖性群体感应（QS）网络的激活以及编码鞭毛蛋白的fliC的抑制。QS网络Rhl分支的激活支持了在慢性感染的CF肺部产生QS分子的观察结果。响应CF气道液体，鞭毛蛋白合成的关闭迅速，且独立于QS以及控制鞭毛基因分级表达的已知调控网络。由于鞭毛蛋白具有高度免疫原性且会被宿主模式识别受体检测到，其抑制可能代表一种适应性反应，使铜绿假单胞菌在CF肺部感染的慢性阶段能够避免被宿主防御机制检测到并被吞噬。
