Speth Cornelia, Rambach Günter, Windisch Andrea, Neurauter Magdalena, Maier Hans, Nagl Markus
Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, A-6020 Innsbruck, Austria.
Christian-Doppler Laboratory for Invasive Fungal Infections, Medical University of Innsbruck, Schöpfstraße 41, A-6020 Innsbruck, Austria.
J Fungi (Basel). 2022 May 20;8(5):535. doi: 10.3390/jof8050535.
N-chlorotaurine (NCT) can be used topically as a well-tolerated anti-infective at different body sites. The aim of this study was to investigate the efficacy of inhaled NCT in a mouse model of fungal pneumonia. Specific pathogen-free female C57BL/6JRj seven-week-old mice were immune-suppressed with cyclophosphamide. After 4 days, the mice were inoculated intranasally with 1.5 × 10E7 spores of or 1.0 × 10E7 spores of . They were randomized and treated three times daily for 10 min with aerosolized 1% NCT or 0.9% sodium chloride starting 1 h after the inoculation. The mice were observed for survival for two weeks, and fungal load, blood inflammation parameters, bronchoalveolar lavage, and histology of organs were evaluated upon their death or at the end of this period. Inhalations were well-tolerated. After challenge with , seven out of the nine mice (77.8%) survived for 15 days in the test group, which was in strong contrast to one out of the nine mice (11.1%) in the control group ( = 0.0049). The count of colony-forming units in the homogenized lung tissues came to 1.60 (1.30; 1.99; median, quartiles) log in the test group and to 4.26 (2.17; 4.53) log in the control group ( = 0.0032). Body weight and temperature, white blood count, and haptoglobin significantly improved with NCT treatment. With , all the mice except for one in the test group died within 4 days without a significant difference from the control group. Inhaled NCT applied early demonstrated a highly significant curative effect in pneumonia, while this could not be shown in pneumonia, probably due to a too high inoculum. Nevertheless, this study for the first time disclosed efficacy of NCT in pneumonia in vivo.
N-氯代牛磺酸(NCT)可作为一种耐受性良好的抗感染剂局部应用于身体不同部位。本研究的目的是在真菌性肺炎小鼠模型中研究吸入NCT的疗效。将无特定病原体的7周龄雌性C57BL/6JRj小鼠用环磷酰胺进行免疫抑制。4天后,给小鼠经鼻接种1.5×10⁷个烟曲霉孢子或1.0×10⁷个白色念珠菌孢子。接种后1小时开始,将它们随机分组,每天用雾化的1% NCT或0.9%氯化钠处理3次,每次10分钟。观察小鼠两周的生存情况,并在其死亡时或该时间段结束时评估真菌载量、血液炎症参数、支气管肺泡灌洗和器官组织学。吸入耐受性良好。用烟曲霉攻击后,试验组9只小鼠中有7只(77.8%)存活15天,这与对照组9只小鼠中的1只(11.1%)形成强烈对比(P = 0.0049)。试验组匀浆肺组织中的菌落形成单位计数为1.60(1.30;1.99;中位数,四分位数)log,对照组为4.26(2.17;4.53)log(P = 0.0032)。NCT治疗后体重、体温、白细胞计数和触珠蛋白显著改善。用白色念珠菌攻击后,试验组除1只小鼠外全部在4天内死亡,与对照组无显著差异。早期应用吸入NCT在烟曲霉肺炎中显示出高度显著的疗效,而在白色念珠菌肺炎中未显示出疗效,可能是由于接种量过高。尽管如此,本研究首次揭示了NCT在体内肺炎中的疗效。