Kinetic Control of Quorum Sensing in Pseudomonas aeruginosa by Multidrug Efflux Pumps,ACS Infectious Diseases

当前位置： X-MOL 学术 › ACS Infect. Dis. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Kinetic Control of Quorum Sensing in Pseudomonas aeruginosa by Multidrug Efflux Pumps
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2017-11-10 00:00:00 , DOI: 10.1021/acsinfecdis.7b00160
David Wolloscheck ₁ , Ganesh Krishnamoorthy ₁ , Jennifer Nguyen ₁ , Helen I. Zgurskaya ₁

Affiliation

Pseudomonas aeruginosa is an important human pathogen, the physiology and virulence of which are under the control of quorum sensing signals. These signals often have dual roles, functioning as toxins to some cells and as oxidative-stress protectors for their producer cells. Hence, their internal and external concentrations should be tightly controlled. In this study, we analyzed the interplay between the multidrug efflux transporters MexEF-OprN and MexG/HI-OpmD in quorum sensing of P. aeruginosa. We found that the two transporters have overlapping substrate specificities but different efficiencies. When overproduced, both MexEF-OprN and MexG/HI-OpmD provide clinical levels of resistance to diverse fluoroquinolones and protect P. aeruginosa against toxic phenazines. However, this similarity is enabled by synergistic interactions with the outer membrane. In hyperporinated cells, MexG/HI-OpmD is saturated by much lower concentrations of fluoroquinolones but is more efficient than MexEF-OprN in efflux of phenazines. Unlike MexEF-OprN, mutational inactivation of MexG/HI-OpmD reduces the levels of pyocyanin and makes P. aeruginosa cells hypersusceptible to phenazines. Our results further show that MexG binds pyocyanin, physically associates with MexHI, and represses the activity of the transporter, revealing a negative regulatory role of this protein. We conclude that differences in kinetic properties of transporters are critical to maintain proper intra- and extracellular concentrations of phenazines and other signaling molecules and that MexG/HI-OpmD controls the steady state in the synthesis and secretion of phenazines.

中文翻译：

多药外排泵对铜绿假单胞菌群体感应的动力学控制

铜绿假单胞菌是重要的人类病原体，其生理和毒力在群体感应信号的控制下。这些信号通常具有双重作用，充当某些细胞的毒素并充当其生产细胞的氧化应激保护剂。因此，应严格控制其内部和外部浓度。在这项研究中，我们分析了铜绿假单胞菌群体感应中多药外排转运蛋白MexEF-OprN和MexG / HI-OpmD之间的相互作用。我们发现这两种转运蛋白具有重叠的底物特异性，但效率不同。当过量生产时，MexEF-OprN和MexG / HI-OpmD均可提供对各种氟喹诺酮类药物的耐药性临床水平，并保护铜绿假单胞菌对抗有毒的吩嗪。但是，这种相似性是通过与外膜的协同相互作用实现的。在超孔化细胞中，MexG / HI-OpmD的氟喹诺酮浓度低得多，但在吩嗪的外排方面比MexEF-OprN更有效。与MexEF-OprN不同，MexG / HI-OpmD的突变失活会降低花青素的水平并使铜绿假单胞菌吩嗪对细胞高度敏感。我们的结果进一步表明，MexG结合了花青素，与MexHI物理缔合，并抑制了转运蛋白的活性，从而揭示了该蛋白的负调控作用。我们得出结论，转运蛋白动力学特性的差异对于维持适当的吩嗪和其他信号分子的细胞内和细胞外浓度至关重要，并且MexG / HI-OpmD控制吩嗪的合成和分泌过程中的稳态。

更新日期：2017-11-10

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11