Institute of Medical Microbiology, University of Szeged, Szeged, Hungary.
In Vivo. 2012 Mar-Apr;26(2):277-85.
One major microbiological problem is the widespread antibiotic resistance. There is an urgent need for new antibiotics and ways to treat multi-drug-resistant infections. Inhibition of bacterial quorum sensing (QS) systems could be an effective alternative in a smuch as they regulate a broad spectrum of cell functions, including, virulence factor production, biofilm organisation and motility. Influx and efflux bacterial systems involved in quorum sensing (QS) are known to depend on the proton motive force (PMF). Thus, a new series of 12 trifluoromethyl ketones (TFs) known to inhibit the PMF, was investigated for effects on the efflux pump of a QS responding bacterium, for its subsequent effect on the response to a QS signal and its direct inhibition of the response to a QS signal.
Chromobacterium violaceum 026 (CV026) was used as the indicator strain to evaluate the QS inhibitory effect of TFs. This strain responds to the presence of short carbon chain acyl-homoserine lactones (AHLs) by the development of a purple pigment. Effect on the QS response of CV026 to externally added AHLs was evaluated. In addition, the specific activity of the TFs on the efflux pump system of the CV026 strain and a wild-type Escherichia coli strain was assessed with the aid of the automated real-time ethidium bromide method.
From the 12 compounds, 6 proved to be effective inhibitors of the QS response by CV026, as well as inhibit the efflux pumps of CV026 and Escherichia coli.
Our results show that TFs have QS inhibitory properties that are mediated through their inhibition of efflux pumps that extrude the noxious QS signal before it reaches its intended target. Because the TFs also inhibit the efflux pump of a pathogenic bacterium, the method used for the evaluation of the TFs in the current study has clinical relevance and may be exploited for the prevention of QS responses of infecting bacteria.
一个主要的微生物学问题是抗生素的广泛耐药性。因此，迫切需要新的抗生素和治疗多药耐药感染的方法。抑制细菌群体感应（QS）系统可能是一种有效的替代方法，因为它们调节广泛的细胞功能，包括毒力因子的产生、生物膜的组织和运动。已知参与群体感应（QS）的细菌内外流系统依赖质子动力势（PMF）。因此，研究了一系列新的 12 种三氟甲基酮（TFs），已知它们抑制 PMF，以研究其对 QS 反应细菌的外排泵的影响，以及随后对 QS 信号的反应及其对 QS 信号的直接抑制作用。
紫罗兰色杆菌 026（CV026）被用作指示菌株，以评估 TF 对 QS 的抑制作用。该菌株通过产生紫色色素来响应短链酰基高丝氨酸内酯（AHLs）的存在。评估 TF 对 CV026 对外加 AHLs 的 QS 反应的影响。此外，借助自动实时溴化乙锭法评估 TF 对 CV026 菌株和野生型大肠杆菌菌株外排泵系统的特异性活性。
在 12 种化合物中，有 6 种被证明能有效抑制 CV026 的 QS 反应，同时抑制 CV026 和大肠杆菌的外排泵。
我们的结果表明，TFs 具有 QS 抑制特性，这是通过抑制外排泵来介导的，外排泵在有害的 QS 信号到达其预期目标之前将其排出。由于 TFs 还抑制了病原菌的外排泵，因此当前研究中用于评估 TFs 的方法具有临床相关性，并可用于防止感染细菌的 QS 反应。
