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Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure
Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second antibiotic th...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Microbiology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313918/ https://www.ncbi.nlm.nih.gov/pubmed/25587013 http://dx.doi.org/10.1128/mBio.02268-14 |
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author | Haaber, Jakob Friberg, Cathrine McCreary, Mark Lin, Richard Cohen, Stanley N. Ingmer, Hanne |
author_facet | Haaber, Jakob Friberg, Cathrine McCreary, Mark Lin, Richard Cohen, Stanley N. Ingmer, Hanne |
author_sort | Haaber, Jakob |
collection | PubMed |
description | Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA] strains). As colistin-induced vancomycin tolerance is reversible, it may not be detected by routine sensitivity testing and may be responsible for treatment failure at vancomycin doses expected to be clinically effective based on such routine testing. Importance Commonly, antibiotic resistance is associated with permanent genetic changes, such as point mutations or acquisition of resistance genes. We show that phenotypic resistance can arise where changes in gene expression result in tolerance to an antibiotic without any accompanying genetic changes. Specifically, methicillin-resistant Staphylococcus aureus (MRSA) behaves like vancomycin-intermediate S. aureus (VISA) upon exposure to colistin, which is currently used against infections by Gram-negative bacteria. Vancomycin is a last-resort drug for treatment of serious S. aureus infections, and VISA is associated with poor clinical prognosis. Phenotypic and reversible resistance will not be revealed by standard susceptibility testing and may underlie treatment failure. |
format | Online Article Text |
id | pubmed-4313918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Society of Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-43139182015-02-02 Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure Haaber, Jakob Friberg, Cathrine McCreary, Mark Lin, Richard Cohen, Stanley N. Ingmer, Hanne mBio Research Article Resistance of Staphylococcus aureus to beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA] strains). As colistin-induced vancomycin tolerance is reversible, it may not be detected by routine sensitivity testing and may be responsible for treatment failure at vancomycin doses expected to be clinically effective based on such routine testing. Importance Commonly, antibiotic resistance is associated with permanent genetic changes, such as point mutations or acquisition of resistance genes. We show that phenotypic resistance can arise where changes in gene expression result in tolerance to an antibiotic without any accompanying genetic changes. Specifically, methicillin-resistant Staphylococcus aureus (MRSA) behaves like vancomycin-intermediate S. aureus (VISA) upon exposure to colistin, which is currently used against infections by Gram-negative bacteria. Vancomycin is a last-resort drug for treatment of serious S. aureus infections, and VISA is associated with poor clinical prognosis. Phenotypic and reversible resistance will not be revealed by standard susceptibility testing and may underlie treatment failure. American Society of Microbiology 2015-01-13 /pmc/articles/PMC4313918/ /pubmed/25587013 http://dx.doi.org/10.1128/mBio.02268-14 Text en Copyright © 2015 Haaber et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Haaber, Jakob Friberg, Cathrine McCreary, Mark Lin, Richard Cohen, Stanley N. Ingmer, Hanne Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure |
title | Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure |
title_full | Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure |
title_fullStr | Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure |
title_full_unstemmed | Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure |
title_short | Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure |
title_sort | reversible antibiotic tolerance induced in staphylococcus aureus by concurrent drug exposure |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313918/ https://www.ncbi.nlm.nih.gov/pubmed/25587013 http://dx.doi.org/10.1128/mBio.02268-14 |
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