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Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization
Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are urgently needed. Adhesion inhibitors are promising new preventive agents that may be less prone to induce resistance, as they do not interfere with the viability of S. aureus and therefore exert l...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002927/ https://www.ncbi.nlm.nih.gov/pubmed/33803564 http://dx.doi.org/10.3390/microorganisms9030631 |
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author | Fernandes de Oliveira, Liliane Maria Steindorff, Marina Darisipudi, Murthy N. Mrochen, Daniel M. Trübe, Patricia Bröker, Barbara M. Brönstrup, Mark Tegge, Werner Holtfreter, Silva |
author_facet | Fernandes de Oliveira, Liliane Maria Steindorff, Marina Darisipudi, Murthy N. Mrochen, Daniel M. Trübe, Patricia Bröker, Barbara M. Brönstrup, Mark Tegge, Werner Holtfreter, Silva |
author_sort | Fernandes de Oliveira, Liliane Maria |
collection | PubMed |
description | Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are urgently needed. Adhesion inhibitors are promising new preventive agents that may be less prone to induce resistance, as they do not interfere with the viability of S. aureus and therefore exert less selection pressure. We identified promising adhesion inhibitors by screening a library of 4208 compounds for their capacity to inhibit S. aureus adhesion to A-549 epithelial cells in vitro in a novel automated, imaging-based assay. The assay quantified DAPI-stained nuclei of the host cell; attached bacteria were stained with an anti-teichoic acid antibody. The most promising candidate, aurintricarboxylic acid (ATA), was evaluated in a novel persistent S. aureus nasal colonization model using a mouse-adapted S. aureus strain. Colonized mice were treated intranasally over 7 days with ATA using a wide dose range (0.5–10%). Mupirocin completely eliminated the bacteria from the nose within three days of treatment. In contrast, even high concentrations of ATA failed to eradicate the bacteria. To conclude, our imaging-based assay and the persistent colonization model provide excellent tools to identify and validate new drug candidates against S. aureus nasal colonization. However, our first tested candidate ATA failed to induce S. aureus decolonization. |
format | Online Article Text |
id | pubmed-8002927 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80029272021-03-28 Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization Fernandes de Oliveira, Liliane Maria Steindorff, Marina Darisipudi, Murthy N. Mrochen, Daniel M. Trübe, Patricia Bröker, Barbara M. Brönstrup, Mark Tegge, Werner Holtfreter, Silva Microorganisms Article Due to increasing mupirocin resistance, alternatives for Staphylococcus aureus nasal decolonization are urgently needed. Adhesion inhibitors are promising new preventive agents that may be less prone to induce resistance, as they do not interfere with the viability of S. aureus and therefore exert less selection pressure. We identified promising adhesion inhibitors by screening a library of 4208 compounds for their capacity to inhibit S. aureus adhesion to A-549 epithelial cells in vitro in a novel automated, imaging-based assay. The assay quantified DAPI-stained nuclei of the host cell; attached bacteria were stained with an anti-teichoic acid antibody. The most promising candidate, aurintricarboxylic acid (ATA), was evaluated in a novel persistent S. aureus nasal colonization model using a mouse-adapted S. aureus strain. Colonized mice were treated intranasally over 7 days with ATA using a wide dose range (0.5–10%). Mupirocin completely eliminated the bacteria from the nose within three days of treatment. In contrast, even high concentrations of ATA failed to eradicate the bacteria. To conclude, our imaging-based assay and the persistent colonization model provide excellent tools to identify and validate new drug candidates against S. aureus nasal colonization. However, our first tested candidate ATA failed to induce S. aureus decolonization. MDPI 2021-03-18 /pmc/articles/PMC8002927/ /pubmed/33803564 http://dx.doi.org/10.3390/microorganisms9030631 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Article Fernandes de Oliveira, Liliane Maria Steindorff, Marina Darisipudi, Murthy N. Mrochen, Daniel M. Trübe, Patricia Bröker, Barbara M. Brönstrup, Mark Tegge, Werner Holtfreter, Silva Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization |
title | Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization |
title_full | Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization |
title_fullStr | Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization |
title_full_unstemmed | Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization |
title_short | Discovery of Staphylococcus aureus Adhesion Inhibitors by Automated Imaging and Their Characterization in a Mouse Model of Persistent Nasal Colonization |
title_sort | discovery of staphylococcus aureus adhesion inhibitors by automated imaging and their characterization in a mouse model of persistent nasal colonization |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002927/ https://www.ncbi.nlm.nih.gov/pubmed/33803564 http://dx.doi.org/10.3390/microorganisms9030631 |
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