Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of <i>Lichtheimia corymbifera</i> and <i>Aspergillus fumigatus</i> Pneumonia

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...

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Main Authors: Cornelia Speth, Günter Rambach, Andrea Windisch, Magdalena Neurauter, Hans Maier, Markus Nagl
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Journal of Fungi
Subjects:
Online Access:https://www.mdpi.com/2309-608X/8/5/535
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author Cornelia Speth
Günter Rambach
Andrea Windisch
Magdalena Neurauter
Hans Maier
Markus Nagl
author_facet Cornelia Speth
Günter Rambach
Andrea Windisch
Magdalena Neurauter
Hans Maier
Markus Nagl
author_sort Cornelia Speth
collection DOAJ
description 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 <i>Lichtheimia corymbifera</i> or 1.0 × 10E7 spores of <i>Aspergillus fumigatus</i>. 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 <i>L. corymbifera</i>, 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 (<i>p</i> = 0.0049). The count of colony-forming units in the homogenized lung tissues came to 1.60 (1.30; 1.99; median, quartiles) log<sub>10</sub> in the test group and to 4.26 (2.17; 4.53) log<sub>10</sub> in the control group (<i>p</i> = 0.0032). Body weight and temperature, white blood count, and haptoglobin significantly improved with NCT treatment. With <i>A. fumigatus</i>, 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 <i>L. corymbifera</i> pneumonia, while this could not be shown in <i>A. fumigatus</i> pneumonia, probably due to a too high inoculum. Nevertheless, this study for the first time disclosed efficacy of NCT in pneumonia in vivo.
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spelling doaj.art-1d99fce6347c44328ab30fe21d8f43ca2023-11-23T11:42:31ZengMDPI AGJournal of Fungi2309-608X2022-05-018553510.3390/jof8050535Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of <i>Lichtheimia corymbifera</i> and <i>Aspergillus fumigatus</i> PneumoniaCornelia Speth0Günter Rambach1Andrea Windisch2Magdalena Neurauter3Hans Maier4Markus Nagl5Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, A-6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, A-6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, A-6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, A-6020 Innsbruck, AustriaINNPATH GmbH-Institute of Pathology, A-6020 Innsbruck, AustriaInstitute of Hygiene and Medical Microbiology, Medical University of Innsbruck, A-6020 Innsbruck, AustriaN-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 <i>Lichtheimia corymbifera</i> or 1.0 × 10E7 spores of <i>Aspergillus fumigatus</i>. 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 <i>L. corymbifera</i>, 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 (<i>p</i> = 0.0049). The count of colony-forming units in the homogenized lung tissues came to 1.60 (1.30; 1.99; median, quartiles) log<sub>10</sub> in the test group and to 4.26 (2.17; 4.53) log<sub>10</sub> in the control group (<i>p</i> = 0.0032). Body weight and temperature, white blood count, and haptoglobin significantly improved with NCT treatment. With <i>A. fumigatus</i>, 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 <i>L. corymbifera</i> pneumonia, while this could not be shown in <i>A. fumigatus</i> pneumonia, probably due to a too high inoculum. Nevertheless, this study for the first time disclosed efficacy of NCT in pneumonia in vivo.https://www.mdpi.com/2309-608X/8/5/535N-chlorotaurinemousepneumoniamolds<i>Lichtheimia</i><i>Aspergillus</i>
spellingShingle Cornelia Speth
Günter Rambach
Andrea Windisch
Magdalena Neurauter
Hans Maier
Markus Nagl
Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of <i>Lichtheimia corymbifera</i> and <i>Aspergillus fumigatus</i> Pneumonia
Journal of Fungi
N-chlorotaurine
mouse
pneumonia
molds
<i>Lichtheimia</i>
<i>Aspergillus</i>
title Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of <i>Lichtheimia corymbifera</i> and <i>Aspergillus fumigatus</i> Pneumonia
title_full Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of <i>Lichtheimia corymbifera</i> and <i>Aspergillus fumigatus</i> Pneumonia
title_fullStr Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of <i>Lichtheimia corymbifera</i> and <i>Aspergillus fumigatus</i> Pneumonia
title_full_unstemmed Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of <i>Lichtheimia corymbifera</i> and <i>Aspergillus fumigatus</i> Pneumonia
title_short Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of <i>Lichtheimia corymbifera</i> and <i>Aspergillus fumigatus</i> Pneumonia
title_sort efficacy of inhaled n chlorotaurine in a mouse model of i lichtheimia corymbifera i and i aspergillus fumigatus i pneumonia
topic N-chlorotaurine
mouse
pneumonia
molds
<i>Lichtheimia</i>
<i>Aspergillus</i>
url https://www.mdpi.com/2309-608X/8/5/535
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