Interconnections of Pseudomonas aeruginosa Quorum-Sensing Systems in Intestinal Permeability and Inflammation.
Interconnections of Pseudomonas aeruginosa Quorum-Sensing Systems in Intestinal Permeability and Inflammation.
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作者：
群体感应（QS）是一种高度保守的微生物通讯机制，基于分泌的信号分子的产生和感应。铜绿假单胞菌是一种具有复杂的相互关联的QS系统控制多种毒力功能的医院内病原体。QS在铜绿假单胞菌发病机制中的相关性已得到充分确立;然而，三种主要QS系统LasR/LasI、MvfR（PqsR）/PqsABCD和RhlR/RhlI的相互调节关系已主要在体外研究。因此，尚不清楚这些关系如何在感染期间转化为宿主环境。在这里，我们使用一组铜绿假单胞菌QS突变体的三个主要的QS系统，以评估在体内肠道炎症和屏障功能的相互联系和贡献。这项工作表明，MvfR，而不是LasR或RhlR，在感染期间促进肠道炎症。相比之下，我们发现铜绿假单胞菌驱动的小鼠肠道通透性由涉及所有三种调节剂的相互连接的QS网络控制，其中MvfR位于LasR和RhlR的上游。这项研究表明了理解感染过程中QS系统相互关系的重要性，并为制定成功的抗毒力策略提供了重要的见解。此外，这项工作提供了一个框架，询问QS系统在生理相关的设置。
Quorum sensing (QS) is a highly conserved microbial communication mechanism based on the production and sensing of secreted signaling molecules. The recalcitrant pathogen Pseudomonas aeruginosa is a problematic nosocomial pathogen with complex interconnected QS systems controlling multiple virulence functions. The relevance of QS in P. aeruginosa pathogenesis is well established; however, the regulatory interrelationships of the three major QS systems, LasR/LasI, MvfR (PqsR)/PqsABCD, and RhlR/RhlI, have been studied primarily in vitro. It is, therefore, unclear how these relationships translate to the host environment during infection. Here, we use a collection of P. aeruginosa QS mutants of the three major QS systems to assess the interconnections and contributions in intestinal inflammation and barrier function in vivo. This work reveals that MvfR, not LasR or RhlR, promotes intestinal inflammation during infection. In contrast, we find that P. aeruginosa-driven murine intestinal permeability is controlled by an interconnected QS network involving all three regulators, with MvfR situated upstream of LasR and RhlR. This study demonstrates the importance of understanding the interrelationships of the QS systems during infection and provides critical insights for developing successful antivirulence strategies. Moreover, this work provides a framework to interrogate QS systems in physiologically relevant settings.
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影响因子：
3.2
作者：
Pesci, EC;Pearson, JP;Iglewski, BH
通讯作者：
Iglewski, BH
影响因子：
8
作者：
Adiliaghdam, Fatemeh;Cavallaro, Paul;Hodin, Richard A.
通讯作者：
Hodin, Richard A.
影响因子：
4.4
作者：
Schuster M;Greenberg EP
通讯作者：
Greenberg EP
影响因子：
5.2
作者：
Hoffman, Lucas R.;Kulasekara, Hemantha D.;Emerson, Julia;Houston, Laura S.;Burns, Jane L.;Ramsey, Bonnie W.;Miller, Samuel I.
通讯作者：
Miller, Samuel I.
影响因子：
16.6
作者：
通讯作者：
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