Antibacterial properties of the CFTR potentiator ivacaftor.
Antibacterial properties of the CFTR potentiator ivacaftor.
复制标题
DOI：
10.1016/j.jcf.2014.02.004
复制
发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Welsh MJ
中科院分区：
文献类型：
--
作者：
Reznikov LR;Abou Alaiwa MH;Dohrn CL;Gansemer ND;Diekema DJ;Stoltz DA;Welsh MJ
对于携带G551D突变的患者，IVAKAFTOR可增加CFTR通道活性并改善肺功能。由于伊伐他在结构上类似于喹诺酮类抗生素，我们检验了伊伐他具有抗菌特性的假设。采用生物发光法、菌落形成单位法和最低抑菌浓度法检测金黄色葡萄球菌、铜绿假单胞菌和多种临床分离微生物的活力。IVacaftor对金黄色葡萄球菌的生物发光有剂量依赖性的抑制作用，并减少了克隆形成单位的数量。我们在铜绿假单胞菌的外膜通透性后观察到了类似但不那么强烈的效应。伊伐他能抑制呼吸道金黄色葡萄球菌和肺炎链球菌的生长，并与抗LAB和呼吸道金黄色葡萄球菌和肺炎链球菌的抗生素呈正相互作用。这些数据表明，iVacaftor显示出抗菌特性，并提出了耐人寻味的可能性，即iVacaftor可能对CF患者具有抗生素作用。
Ivacaftor increases CFTR channel activity and improves pulmonary function for individuals bearing a G551D mutation. Because ivacaftor structurally resembles quinolone antibiotics, we tested the hypothesis that ivacaftor possesses antibacterial properties. Bioluminescence, colony forming unit, and minimal inhibitory concentration assays were used to assess viability of Staphylococcus aureus, Pseudomonas aeruginosa and multiple clinical microbial isolates. Ivacaftor induced a dose-dependent reduction in bioluminescence of S. aureus and decreased the number of colony forming units. We observed a similar but less robust effect in P. aeruginosa following outer membrane permeabilization. Ivacaftor inhibited the growth of respiratory isolates of S. aureus and Streptococcus pneumoniae and exhibited positive interactions with antibiotics against lab and respiratory strains of S. aureus and S. pneumoniae. These data indicate that ivacaftor exhibits antibacterial properties and raise the intriguing possibility that ivacaftor might have an antibiotic effect in people with CF.