In the absence of effector proteins, the Pseudomonas aeruginosa type three secretion system needle tip complex contributes to lung injury and systemic inflammatory responses.
In the absence of effector proteins, the Pseudomonas aeruginosa type three secretion system needle tip complex contributes to lung injury and systemic inflammatory responses.
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DOI：
10.1371/journal.pone.0081792
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Alvarez DF
中科院分区：
文献类型：
--
作者：
Audia JP;Lindsey AS;Housley NA;Ochoa CR;Zhou C;Toba M;Oka M;Annamdevula NS;Fitzgerald MS;Frank DW;Alvarez DF
本文描述了铜绿假单胞菌3型分泌系统（T3SS）针尖复合体蛋白（PcrV）在引起肺内皮损伤中的致病作用。我们首先建立了铜绿假单胞菌野生型菌株PA103引起肺炎致败血症和远端器官功能障碍的模型。有趣的是，缺乏其两种已知分泌效应物ExoU和ExoT的PA103衍生菌株[表示PA103 （ΔU/ΔT）]也会导致败血症和中度远端器官损伤，而缺乏T3SS针尖复合物组装蛋白的等基因PA103菌株[表示PA103 （ΔPcrV）)则不会。PA103 （ΔU/ΔT）感染引起中性粒细胞内流到肺实质，肺内皮损伤和远端器官损伤（使人联想到败血症）。相比之下，PA103 （ΔPcrV）感染引起名义中性粒细胞浸润和肺内皮损伤，但未引起远端器官损伤。我们利用培养的大鼠肺微血管内皮细胞（PMVECs）进一步研究了T3SS针尖复合物的致病机制，并揭示了感染的两阶段、时间性质。在接种后5小时（早期感染），PA103 （ΔU/ΔT）通过扰乱肌动蛋白细胞骨架引发PMVEC屏障破坏，并且以细胞死亡无关的方式进行。相反，PA103 （ΔPcrV）感染不会引起早期PMVEC屏障破坏。在接种24小时后（后期感染），PA103 （ΔU/ΔT）诱导PMVEC损伤和死亡，并表现出凋亡成分。虽然PA103 （ΔPcrV）感染诱导晚期PMVEC损伤和死亡，但其程度较弱。PA103 （ΔU/ΔT）和PA103 （ΔPcrV）突变体以相似的速度生长，并且能够在接种后同样粘附在PMVECs上，这表明观察到的损伤和屏障破坏的差异可能归因于宿主细胞附着后T3SS针尖复合物介导的致病性差异。总之，这些感染数据表明，T3SS针尖复合物和/或其他未定义的分泌效应物是铜绿假单胞菌肺炎诱导肺内皮屏障破坏的重要决定因素。
Herein we describe a pathogenic role for the Pseudomonas aeruginosa type three secretion system (T3SS) needle tip complex protein, PcrV, in causing lung endothelial injury. We first established a model in which P. aeruginosa wild type strain PA103 caused pneumonia-induced sepsis and distal organ dysfunction. Interestingly, a PA103 derivative strain lacking its two known secreted effectors, ExoU and ExoT [denoted PA103 (ΔU/ΔT)], also caused sepsis and modest distal organ injury whereas an isogenic PA103 strain lacking the T3SS needle tip complex assembly protein [denoted PA103 (ΔPcrV)] did not. PA103 (ΔU/ΔT) infection caused neutrophil influx into the lung parenchyma, lung endothelial injury, and distal organ injury (reminiscent of sepsis). In contrast, PA103 (ΔPcrV) infection caused nominal neutrophil infiltration and lung endothelial injury, but no distal organ injury. We further examined pathogenic mechanisms of the T3SS needle tip complex using cultured rat pulmonary microvascular endothelial cells (PMVECs) and revealed a two-phase, temporal nature of infection. At 5-hours post-inoculation (early phase infection), PA103 (ΔU/ΔT) elicited PMVEC barrier disruption via perturbation of the actin cytoskeleton and did so in a cell death-independent manner. Conversely, PA103 (ΔPcrV) infection did not elicit early phase PMVEC barrier disruption. At 24-hours post-inoculation (late phase infection), PA103 (ΔU/ΔT) induced PMVEC damage and death that displayed an apoptotic component. Although PA103 (ΔPcrV) infection induced late phase PMVEC damage and death, it did so to an attenuated extent. The PA103 (ΔU/ΔT) and PA103 (ΔPcrV) mutants grew at similar rates and were able to adhere equally to PMVECs post-inoculation indicating that the observed differences in damage and barrier disruption are likely attributable to T3SS needle tip complex-mediated pathogenic differences post host cell attachment. Together, these infection data suggest that the T3SS needle tip complex and/or another undefined secreted effector(s) are important determinants of P. aeruginosa pneumonia-induced lung endothelial barrier disruption.
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影响因子：
8.7
作者：
Broz P;Monack DM
通讯作者：
Monack DM
DOI：
10.1083/jcb.147.3.683
发表时间：
1999-11-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Blocker A;Gounon P;Larquet E;Niebuhr K;Cabiaux V;Parsot C;Sansonetti P
通讯作者：
Sansonetti P
影响因子：
3.1
作者：
Allmond, LR;Karaca, TJ;Sawa, T
通讯作者：
Sawa, T
影响因子：
3.6
作者：
Auvin, S;Collet, FS;Guery, BP
通讯作者：
Guery, BP
影响因子：
5.8
作者：
Boyer, S;Faure, K;Guery, BP
通讯作者：
Guery, BP