High variability in quorum quenching and growth inhibition by furanone C-30 in Pseudomonas aeruginosa clinical isolates from cystic fibrosis patients
High variability in quorum quenching and growth inhibition by furanone C-30 in Pseudomonas aeruginosa clinical isolates from cystic fibrosis patients
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DOI：
10.1093/femspd/ftv040
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发表时间：
2015-08-01
影响因子：
3.3
通讯作者：
Wood, Thomas K.
中科院分区：
文献类型：
--
作者：
Garcia-Contreras, Rodolfo;Perez-Eretza, Berenice;Wood, Thomas K.
铜绿假单胞菌定植于囊性纤维化患者的肺部，造成严重损害。该细菌对抗生素具有内在抗性，并对新的抗菌剂具有抗性，其毒力受群体感应反应控制。因此，已经提出通过群体淬灭而不是抑制其生长来减弱其毒力以使抗性最小化;然而，可以通过导致增加外排的突变来实现对典型群体淬灭剂呋喃酮C-30的抗性。在目前的工作中，C-30的效果在QS-controlled毒力因子弹性蛋白酶和绿脓菌素的衰减进行了研究，在50株囊性纤维化患者。结果表明，弹性蛋白酶和绿脓菌素的表达存在高度变异性，并且存在许多天然抗性C-30菌株。我们报告说，在这些菌株中的C-30耐药的主要机制不是由于增强外排，但缺乏渗透性。此外，C-30强烈抑制几个菌株的生长研究，从而施加高选择压力的产生阻力。
Pseudomonas aeruginosa colonizes the lungs of cystic fibrosis patients causing severe damage. This bacterium is intrinsically resistant to antibiotics and shows resistance against new antimicrobials and its virulence is controlled by the quorum-sensing response. Thus, attenuating its virulence by quorum quenching instead of inhibiting its growth has been proposed to minimize resistance; however, resistance against the canonical quorum quencher furanone C-30 can be achieved by mutations leading to increased efflux. In the present work, the effect of C-30 in the attenuation of the QS-controlled virulence factors elastase and pyocyanin was investigated in 50 isolates from cystic fibrosis patients. The results demonstrate that there is a high variability in the expression of both elastase and pyocyanin and that there are many naturally resistant C-30 strains. We report that the main mechanism of C-30 resistance in these strains was not due to enhanced efflux but a lack of permeability. Moreover, C-30 strongly inhibited the growth of several of the isolates studied, thus imposing high selective pressure for the generation of resistance.