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在肺上皮细胞存在的情况下,N-氯代牛磺酸的杀菌活性可得到增强。

Microbicidal activity of N-chlorotaurine can be enhanced in the presence of lung epithelial cells.

作者信息

Leiter Hannes, Toepfer Stephanie, Messner Petra, Rabensteiner Marion, Gostner Johanna M, Lackner Michaela, Hermann Martin, Nagl Markus

机构信息

Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Schöpfstr. 41, A-6020 Innsbruck, Austria.

Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Schöpfstr. 41, A-6020 Innsbruck, Austria; Division of Medical Biochemistry, Medical University of Innsbruck, Austria.

出版信息

J Cyst Fibros. 2020 Nov;19(6):1011-1017. doi: 10.1016/j.jcf.2020.03.005. Epub 2020 Mar 20.

Abstract

BACKGROUND

N-chlorotaurine (NCT) is an endogenous active chlorine compound that can be used as an antiseptic and anti-infective in different body regions. Recently, tolerability of inhaled NCT has been demonstrated in humans so that it is of interest for future treatment of cystic fibrosis. In the present study, we tested the bactericidal and fungicidal activity of NCT in different lung cell culture models.

METHODS

Bacteria (Staphylococcus aureus, Pseudomonas aeruginosa) and fungi (Candida albicans, Exophiala dermatitidis) were co-incubated with lung epithelial cell cultures, and after 4 h NCT was added. After different incubation times, aliquots were removed and quantitative cultures were performed.

RESULTS

NCT at the therapeutically applied concentration of 1% (55 mM) completely killed the test pathogens within 15 - 30 min at 20 °C and at 37 °C. Killing by 0.3% NCT lasted up to 4 h dependent on the pathogen at 20 °C and up to 1 h at 37 °C. 0.1% NCT was the threshold concentration for killing since this amount of oxidation capacity was consumed by reactions with the organic compounds of the medium within 3 h (20 °C) and 0.5 h (37 °C).

CONCLUSIONS

NCT in therapeutic concentration demonstrated its microbicidal activity in the presence of lung epithelial cells. Remarkably, particularly the fungicidal activity was higher under these conditions than in phosphate buffer. This can be explained by formation of the stronger microbicidal monochloramine in equilibrium by transchlorination. The results suggest the suitability of NCT as inhalation medication in the lung.

摘要

背景

N - 氯代牛磺酸(NCT)是一种内源性活性氯化合物,可在身体不同部位用作防腐剂和抗感染剂。最近,已在人体中证明了吸入NCT的耐受性,因此它对未来囊性纤维化的治疗具有重要意义。在本研究中,我们在不同的肺细胞培养模型中测试了NCT的杀菌和杀真菌活性。

方法

将细菌(金黄色葡萄球菌、铜绿假单胞菌)和真菌(白色念珠菌、皮炎外瓶霉)与肺上皮细胞培养物共同孵育,4小时后加入NCT。在不同的孵育时间后,取出等分试样并进行定量培养。

结果

在20°C和37°C下,治疗应用浓度为1%(55 mM)的NCT在15 - 30分钟内完全杀死了测试病原体。在20°C下,0.3% NCT的杀菌作用持续长达4小时,取决于病原体,在37°C下持续长达1小时。0.1% NCT是杀菌的阈值浓度,因为该氧化能力的量在3小时(20°C)和0.5小时(37°C)内被与培养基有机化合物的反应消耗。

结论

治疗浓度的NCT在肺上皮细胞存在下表现出其杀微生物活性。值得注意的是,特别是在这些条件下的杀真菌活性比在磷酸盐缓冲液中更高。这可以通过转氯作用在平衡中形成更强的杀微生物一氯胺来解释。结果表明NCT适合作为肺部吸入药物。

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