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Microbicidal activity of N-chlorotaurine can be enhanced in the presence of lung epithelial cells
Journal of Cystic Fibrosis ( IF 5.4 ) Pub Date : 2020-11-01 , DOI: 10.1016/j.jcf.2020.03.005
Hannes Leiter 1 , Stephanie Toepfer 2 , Petra Messner 1 , Marion Rabensteiner 1 , Johanna M Gostner 3 , Michaela Lackner 1 , Martin Hermann 4 , Markus Nagl 1
Affiliation  

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.

中文翻译:

N-氯牛磺酸的杀菌活性在肺上皮细胞的存在下可以增强

背景技术 N-氯牛磺酸(NCT)是一种内源性活性氯化合物,可在身体不同部位起到杀菌和抗感染作用。最近,吸入 NCT 的耐受性已在人类中得到证实,因此它对未来治疗囊性纤维化很感兴趣。在本研究中,我们测试了 NCT 在不同肺细胞培养模型中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、皮炎外管菌)与肺上皮细胞培养物共培养,4小时后加入NCT。在不同的温育时间后,取出等分试样并进行定量培养。结果 在 1% (55 mM) 的治疗应用浓度下,NCT 在 20 °C 和 37 °C 下在 15 - 30 分钟内完全杀死了测试病原体。根据病原体,0.3% NCT 的杀死持续时间长达 4 小时,具体取决于病原体在 20 °C 下的情况,在 37 °C 下持续时间长达 1 小时。0.1% NCT 是杀死的阈值浓度,因为在 3 小时(20 摄氏度)和 0.5 小时(37 摄氏度)内与培养基的有机化合物反应消耗了这一氧化能力。结论 治疗浓度的 NCT 在肺上皮细胞的存在下证明了其杀菌活性。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。这可以通过转氯化作用在平衡中形成更强的杀菌一氯胺来解释。结果表明 NCT 作为肺部吸入药物的适用性。1% NCT 是杀死的阈值浓度,因为在 3 小时(20°C)和 0.5 小时(37°C)内与培养基中的有机化合物反应消耗了这一氧化能力。结论 治疗浓度的 NCT 在肺上皮细胞的存在下证明了其杀菌活性。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。这可以通过转氯化作用在平衡中形成更强的杀菌一氯胺来解释。结果表明 NCT 作为肺部吸入药物的适用性。1% NCT 是杀死的阈值浓度,因为在 3 小时(20°C)和 0.5 小时(37°C)内与培养基中的有机化合物反应消耗了这一氧化能力。结论 治疗浓度的 NCT 在肺上皮细胞的存在下证明了其杀菌活性。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。这可以通过转氯化作用在平衡中形成更强的杀菌一氯胺来解释。结果表明 NCT 作为肺部吸入药物的适用性。结论 治疗浓度的 NCT 在肺上皮细胞的存在下证明了其杀菌活性。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。这可以通过转氯化作用在平衡中形成更强的杀菌一氯胺来解释。结果表明 NCT 作为肺部吸入药物的适用性。结论 治疗浓度的 NCT 在肺上皮细胞的存在下证明了其杀菌活性。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。这可以通过转氯化作用在平衡中形成更强的杀菌一氯胺来解释。结果表明 NCT 作为肺部吸入药物的适用性。
更新日期:2020-11-01
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