Characterization of cell-to-cell signaling-deficient Pseudomonas aeruginosa strains colonizing intubated patients
Characterization of cell-to-cell signaling-deficient Pseudomonas aeruginosa strains colonizing intubated patients
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DOI：
10.1128/jcm.42.2.554-562.2004
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发表时间：
2004-02-01
影响因子：
9.4
通讯作者：
van Delden, C
中科院分区：
文献类型：
--
作者：
Dénervaud, V;TuQuoc, P;van Delden, C
涉及N-酰基高丝氨酸内酯化合物的细胞间信号转导被称为自身诱导物(AIS)，对铜绿假单胞菌的毒力因子的产生和生物膜的形成具有重要作用。为了确定细胞间信号在机械通气患者定植过程中的重要性，我们收集了13例患者的442株铜绿假单胞菌。表型鉴定表明，81%的菌株产生依赖AI的毒力因子弹性蛋白酶、蛋白酶和鼠李糖脂。我们鉴定了9株具有不同基因特征的铜绿假单胞菌。这些菌株中有6株在体外产生AIS[N-丁酰基-高丝氨酸内酯或N-(3-氧代-十二酰基)-高丝氨酸内酯]和胞外毒力因子(弹性蛋白酶、总外切酶、鼠李糖脂、氰化氢或绿色素)。在9株菌株中，有3株在产生AIS和胞外毒力因子方面存在缺陷。其中两株LasR和RhlR基因均存在突变缺陷，分别编码N-酰基高丝氨酸内酯依赖的转录调控因子LasR和RhlR。这些AI缺陷菌株中的第三个只在LasR基因上发生突变。我们的观察表明，大多数但不是所有定植于插管患者的菌株都能够产生毒力因子，影响细胞间信号通路的突变优先位于转录调节基因中。
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.