Furoxan一氧化氮供体分散<i>铜绿假单胞菌</i>生物膜，加速生长，并抑制吡啶酮的生产,ACS Chemical Biology

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Furoxan一氧化氮供体分散铜绿假单胞菌生物膜，加速生长，并抑制吡啶酮的生产
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2017-06-29 00:00:00 , DOI: 10.1021/acschembio.7b00256
Wee Han Poh ₁ , Nicolas Barraud ₂ , Stefano Guglielmo ₃ , Loretta Lazzarato ₃ , Barbara Rolando ₃ , Roberta Fruttero ₃ , Scott A. Rice _{1,

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Affiliation

一氧化氮（NO）作为生物膜扩散的信号的使用已显示出可增加许多生物膜对抗生素的敏感性，从而促进其根除。通过使用具有不同动力学和NO释放特性的NO供体可以实现NO向生物膜的传递，NO供体的动力学和NO释放特性会影响其作为生物膜控制剂的功效。在这项研究中，评估了三种呋喃喃衍生物的动力学。这些NO供体对铜绿假单胞菌的药理学特征是起效较慢且作用持续时间长，具有有利的药理作用生长，生物膜发育和扩散也得到了表征。显示出快速NO释放速率的化合物LL4254诱导生物膜的扩散约为200μM。尽管LL4212和LL4216的NO释放速度较慢，但当以较高的浓度使用时，在相同的处理条件下，这两种化合物均可诱导生物膜的分散。此外，发现LL4212和LL4216可以促进铁限制基本培养基中的铜绿假单胞菌生长，从而导致更快的生物膜形成速率和葡萄糖利用率，并最终通过碳饥饿导致生物膜细胞的早期分散。高浓度的LL4216还通过依赖于NO _x和NO _x抑制了铁载体吡啶酮的生产超过50倍。独立机制。呋喃喃对生长和嘧啶含量的影响似乎是由NO依赖性机制介导的，表明呋喃喃除了释放NO和亚硝酸盐外还具有功能活性。总的来说，这项研究表明，呋喃喃类药物的次级作用是将其用作释放NO的分散剂的重要考虑因素，并且这些化合物有可能被重新设计为吡over定抑制剂。

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Furoxan Nitric Oxide Donors Disperse Pseudomonas aeruginosa Biofilms, Accelerate Growth, and Repress Pyoverdine Production

The use of nitric oxide (NO) as a signal for biofilm dispersal has been shown to increase the susceptibility of many biofilms to antibiotics, promoting their eradication. The delivery of NO to biofilms can be achieved by using NO donors with different kinetics and properties of NO release that can influence their efficacy as biofilm control agents. In this study, the kinetics of three furoxan derivatives were evaluated. The effects of these NO donors, which have an advantageous pharmacological profile of slower onset with an extended duration of action, on Pseudomonas aeruginosa growth, biofilm development, and dispersal were also characterized. Compound LL4254, which showed a fast rate of NO release, induced biofilm dispersal at approximately 200 μM. While LL4212 and LL4216 have a slower rate of NO release, both compounds could induce biofilm dispersal, under the same treatment conditions, when used at higher concentrations. In addition, LL4212 and LL4216 were found to promote P. aeruginosa growth in iron-limited minimal medium, leading to a faster rate of biofilm formation and glucose utilization, and ultimately resulted in early dispersal of biofilm cells through carbon starvation. High concentrations of LL4216 also repressed production of the siderophore pyoverdine by more than 50-fold, via both NO_x-dependent and NO_x-independent mechanisms. The effects on growth and pyoverdine levels exerted by the furoxans appeared to be mediated by NO-independent mechanisms, suggesting functional activities of furoxans in addition to their release of NO and nitrite. Overall, this study reveals that secondary effects of furoxans are important considerations for their use as NO-releasing dispersal agents and that these compounds could be potentially redesigned as pyoverdine inhibitors.

更新日期：2017-06-30

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