Surfactant phospholipids act as molecular switches for premature induction of quorum sensing-dependent virulence in Pseudomonas aeruginosa.
Surfactant phospholipids act as molecular switches for premature induction of quorum sensing-dependent virulence in Pseudomonas aeruginosa.
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DOI：
10.1080/21505594.2020.1809327
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发表时间：
2020-12
期刊：
影响因子：
5.2
通讯作者：
Lau GW
中科院分区：
文献类型：
--
作者：
Kuang Z;Bennett RC;Lin J;Hao Y;Zhu L;Akinbi HT;Lau GW
许多革兰氏阴性细菌病原体的毒力行为由群体感应（quorum-sensing，QS）控制，群体感应是一种通过产生和检测细胞外信号分子依赖于群体密度的基因调控的分级系统。虽然在体外条件下进行了广泛的研究，但QS系统对生理相关宿主环境的适应性尚未完全了解。在这项研究中，我们研究了肺环境的影响，铜绿假单胞菌毒力因子的调节QS在小鼠急性肺炎模型。当在实验室条件下在溶原肉汤中培养时，野生型铜绿假单胞菌菌株PAO 1在从晚期指数生长期过渡到稳定生长期期间开始表达QS调节的毒力因子弹性蛋白酶B（LasB）和鼠李糖脂（RhlA）。相反，在急性肺炎期间以及当在小鼠支气管肺泡灌洗液（BALF）中培养时，低种群密度的指数期PAO 1细菌过早地表达QS调节基因lasI-lasR和rhlI-rhlR及其下游毒力基因lasB和rhlA。进一步分析表明，表面活性剂磷脂是BALF中诱导N-（3-氧代十二烷酰基）-L-高丝氨酸内酯（C12-HSL）合成的主要成分，其触发LasB和RhlA的过早表达。酚提取物和磷脂酶A2消化都消除了小鼠BALF促进LasB和RhlA表达的能力。相反，提供主要的表面活性剂磷脂二棕榈酰磷脂酰胆碱（DPPC）恢复两个毒力因子的表达。总的来说，我们的研究表明铜绿假单胞菌通过识别肺表面活性物质磷脂来调节其QS以协调急性肺炎期间毒力因子的表达。
The virulence behaviors of many Gram-negative bacterial pathogens are governed by quorum-sensing (QS), a hierarchical system of gene regulation that relies on population density by producing and detecting extracellular signaling molecules. Although extensively studied under in vitro conditions, adaptation of QS system to physiologically relevant host environment is not fully understood. In this study, we investigated the influence of lung environment on the regulation of Pseudomonas aeruginosa virulence factors by QS in a mouse model of acute pneumonia. When cultured under laboratory conditions in lysogeny broth, wild-type P. aeruginosa strain PAO1 began to express QS-regulated virulence factors elastase B (LasB) and rhamnolipids (RhlA) during transition from late-exponential into stationary growth phase. In contrast, during acute pneumonia as well as when cultured in mouse bronchial alveolar lavage fluids (BALF), exponential phase PAO1 bacteria at low population density prematurely expressed QS regulatory genes lasI-lasR and rhlI-rhlR and their downstream virulence genes lasB and rhlA. Further analysis indicated that surfactant phospholipids were the primary components within BALF that induced the synthesis of N-(3-oxododecanoyl)-L-homoserine lactone (C12-HSL), which triggered premature expression of LasB and RhlA. Both phenol extraction and phospholipase A2 digestion abolished the ability of mouse BALF to promote LasB and RhlA expression. In contrast, provision of the major surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) restored the expression of both virulence factors. Collectively, our study demonstrates P. aeruginosa modulates its QS to coordinate the expression of virulence factors during acute pneumonia by recognizing pulmonary surfactant phospholipids.
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影响因子：
4.6
作者：
Ghidoni R;Caretti A;Signorelli P
通讯作者：
Signorelli P
DOI：
10.1056/nejmra0910061
发表时间：
2010-12-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Fahy JV;Dickey BF
通讯作者：
Dickey BF
影响因子：
5.7
作者：
Holm A;Magnusson KE;Vikström E
通讯作者：
Vikström E
DOI：
10.1165/rcmb.2009-0174oc
发表时间：
2010-06-01
影响因子：
6.4
作者：
Becker, Katrin Anne;Riethmueller, Joachim;Gulbins, Erich
通讯作者：
Gulbins, Erich
影响因子：
3.9
作者：
Holweg, Alexander;Schnare, Markus;Gessner, Andre
通讯作者：
Gessner, Andre