Dénervaud Valérie, TuQuoc Patrick, Blanc Dominique, Favre-Bonté Sabine, Krishnapillai Viji, Reimmann Cornelia, Haas Dieter, van Delden Christian
Institut de Microbiologie Fondamentale, Université de Lausanne, CH-1015 Lausanne, Switzerland.
J Clin Microbiol. 2004 Feb;42(2):554-62. doi: 10.1128/JCM.42.2.554-562.2004.
Cell-to-cell signaling involving N-acyl-homoserine lactone compounds termed autoinducers (AIs) is instrumental to virulence factor production and biofilm development by Pseudomonas aeruginosa. In order to determine the importance of cell-to-cell signaling during the colonization of mechanically ventilated patients, we collected 442 P. aeruginosa pulmonary isolates from 13 patients. Phenotypic characterization showed that 81% of these isolates produced the AI-dependent virulence factors elastase, protease, and rhamnolipids. We identified nine genotypically distinct P. aeruginosa strains. Six of these strains produced AIs [N-butanoyl-homoserine lactone or N-(3-oxo-dodecanoyl)-homoserine lactone] and extracellular virulence factors (elastase, total exoprotease, rhamnolipid, hydrogen cyanide, or pyocyanin) in vitro. Three of the nine strains were defective in the production of both AIs and extracellular virulence factors. Two of these strains had mutational defects in both the lasR and rhlR genes, which encode the N-acyl-homoserine lactone-dependent transcriptional regulators LasR and RhlR, respectively. The third of these AI-deficient strains was only mutated in the lasR gene. Our observations suggest that most, but not all, strains colonizing intubated patients are able to produce virulence factors and that mutations affecting the cell-to-cell signaling circuit are preferentially located in the transcriptional regulator genes.
涉及被称为自诱导物（AIs）的N-酰基高丝氨酸内酯化合物的细胞间信号传导，对铜绿假单胞菌产生毒力因子和形成生物膜起着重要作用。为了确定机械通气患者定植过程中细胞间信号传导的重要性，我们从13名患者中收集了442株铜绿假单胞菌肺部分离株。表型特征显示，这些分离株中有81%产生依赖AI的毒力因子弹性蛋白酶、蛋白酶和鼠李糖脂。我们鉴定出9种基因型不同的铜绿假单胞菌菌株。其中6种菌株在体外产生AIs [N-丁酰高丝氨酸内酯或N-（3-氧代十二烷酰）-高丝氨酸内酯] 和细胞外毒力因子（弹性蛋白酶、总胞外蛋白酶、鼠李糖脂、氰化氢或绿脓菌素）。9种菌株中有3种在产生AIs和细胞外毒力因子方面存在缺陷。其中2种菌株在分别编码N-酰基高丝氨酸内酯依赖性转录调节因子LasR和RhlR的lasR和rhlR基因中都有突变缺陷。这些AI缺陷菌株中的第三种仅在lasR基因中发生了突变。我们的观察结果表明，定植于插管患者的大多数（但不是全部）菌株能够产生毒力因子，并且影响细胞间信号传导回路的突变优先位于转录调节基因中。
