Reversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure

ABSTRACT 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 an...

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Autores principales:	Jakob Haaber, Cathrine Friberg, Mark McCreary, Richard Lin, Stanley N. Cohen, Hanne Ingmer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7edd40160da94fe792d0bc0d0d48499a
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spelling	oai:doaj.org-article:7edd40160da94fe792d0bc0d0d48499a2021-11-15T15:41:19ZReversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure10.1128/mBio.02268-142150-7511https://doaj.org/article/7edd40160da94fe792d0bc0d0d48499a2015-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02268-14https://doaj.org/toc/2150-7511ABSTRACT 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.Jakob HaaberCathrine FribergMark McCrearyRichard LinStanley N. CohenHanne IngmerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 1 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jakob Haaber Cathrine Friberg Mark McCreary Richard Lin Stanley N. Cohen Hanne Ingmer Reversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure
description	ABSTRACT 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	article
author	Jakob Haaber Cathrine Friberg Mark McCreary Richard Lin Stanley N. Cohen Hanne Ingmer
author_facet	Jakob Haaber Cathrine Friberg Mark McCreary Richard Lin Stanley N. Cohen Hanne Ingmer
author_sort	Jakob Haaber
title	Reversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure
title_short	Reversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure
title_full	Reversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure
title_fullStr	Reversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure
title_full_unstemmed	Reversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure
title_sort	reversible antibiotic tolerance induced in <named-content content-type="genus-species">staphylococcus aureus</named-content> by concurrent drug exposure
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/7edd40160da94fe792d0bc0d0d48499a
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Reversible Antibiotic Tolerance Induced in <named-content content-type="genus-species">Staphylococcus aureus</named-content> by Concurrent Drug Exposure

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