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CFTR 增强剂依伐卡托的抗菌特性。

Antibacterial properties of the CFTR potentiator ivacaftor.

作者信息

Reznikov Leah R, Abou Alaiwa Mahmoud H, Dohrn Cassie L, Gansemer Nick D, Diekema Daniel J, Stoltz David A, Welsh Michael J

机构信息

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States.

Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States; Howard Hughes Medical Institute (HHMI), University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States; Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52333, United States.

出版信息

J Cyst Fibros. 2014 Sep;13(5):515-9. doi: 10.1016/j.jcf.2014.02.004. Epub 2014 Mar 5.

Abstract

BACKGROUND

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.

METHODS

Bioluminescence, colony forming unit, and minimal inhibitory concentration assays were used to assess viability of Staphylococcus aureus, Pseudomonas aeruginosa and multiple clinical microbial isolates.

RESULTS

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.

CONCLUSION

These data indicate that ivacaftor exhibits antibacterial properties and raise the intriguing possibility that ivacaftor might have an antibiotic effect in people with CF.

摘要

背景

依伐卡托可增加携带G551D突变个体的囊性纤维化跨膜传导调节因子(CFTR)通道活性并改善肺功能。由于依伐卡托在结构上类似于喹诺酮类抗生素,我们检验了依伐卡托具有抗菌特性这一假设。

方法

采用生物发光、菌落形成单位和最低抑菌浓度测定法评估金黄色葡萄球菌、铜绿假单胞菌及多种临床微生物分离株的生存能力。

结果

依伐卡托可使金黄色葡萄球菌的生物发光呈剂量依赖性降低,并减少菌落形成单位数量。在外膜通透性增加后,我们在铜绿假单胞菌中观察到了类似但较弱的作用。依伐卡托可抑制金黄色葡萄球菌和肺炎链球菌呼吸道分离株的生长,并与针对金黄色葡萄球菌和肺炎链球菌实验室菌株及呼吸道菌株的抗生素表现出协同作用。

结论

这些数据表明依伐卡托具有抗菌特性,并提出了一个有趣的可能性,即依伐卡托可能对囊性纤维化患者具有抗生素作用。

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