Antibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>

ABSTRACT Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virule...

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Autores principales:	Wilhelm Paulander, Anders Nissen Varming, Kristoffer T. Bæk, Jakob Haaber, Dorte Frees, Hanne Ingmer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7d8517718da2476ba990b27f92366cda
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spelling	oai:doaj.org-article:7d8517718da2476ba990b27f92366cda2021-11-15T15:39:11ZAntibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>10.1128/mBio.00459-122150-7511https://doaj.org/article/7d8517718da2476ba990b27f92366cda2012-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00459-12https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly increases the agr-mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among community-acquired S. aureus strains. Importantly, agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital-acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus. IMPORTANCE Staphylococcus aureus is the most frequently isolated pathogen in intensive care units and a common cause of nosocomial infections, resulting in a high degree of morbidity and mortality. Surprisingly, a large fraction (15 to 60%) of hospital-isolated S. aureus strains are agr defective and lack the main quorum-sensing-controlled virulence regulatory system. This is a problem, as agr-defective strains are associated with a mortality level in bacteremic infections and a probability of glycopeptide resistance greater than those of other strains. We show here that agr-negative strains have a fitness advantage over agr-positive strains in the presence of sublethal concentrations of some antibiotics and that the fitness defect of agr-positive cells is caused by antibiotic-mediated expression of the agr effector molecule RNAIII. These results offer an explanation of the frequent isolation of agr-defective S. aureus strains in hospitals and will influence how we treat S. aureus infections.Wilhelm PaulanderAnders Nissen VarmingKristoffer T. BækJakob HaaberDorte FreesHanne IngmerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 6 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Wilhelm Paulander Anders Nissen Varming Kristoffer T. Bæk Jakob Haaber Dorte Frees Hanne Ingmer Antibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>
description	ABSTRACT Staphylococcus aureus is a human commensal that at times turns into a serious bacterial pathogen causing life-threatening infections. For the delicate control of virulence, S. aureus employs the agr quorum-sensing system that, via the intracellular effector molecule RNAIII, regulates virulence gene expression. We demonstrate that the presence of the agr locus imposes a fitness cost on S. aureus that is mediated by the expression of RNAIII. Further, we show that exposure to sublethal levels of the antibiotics ciprofloxacin, mupirocin, and rifampin, each targeting separate cellular functions, markedly increases the agr-mediated fitness cost by inducing the expression of RNAIII. Thus, the extensive use of antibiotics in hospitals may explain why agr-negative variants are frequently isolated from hospital-acquired S. aureus infections but rarely found among community-acquired S. aureus strains. Importantly, agr deficiency correlates with increased duration of and mortality due to bacteremia during antibiotic treatment and with a higher frequency of glycopeptide resistance than in agr-carrying strains. Our results provide an explanation for the frequent isolation of agr-defective strains from hospital-acquired S. aureus infections and suggest that the adaptability of S. aureus to antibiotics involves the agr locus. IMPORTANCE Staphylococcus aureus is the most frequently isolated pathogen in intensive care units and a common cause of nosocomial infections, resulting in a high degree of morbidity and mortality. Surprisingly, a large fraction (15 to 60%) of hospital-isolated S. aureus strains are agr defective and lack the main quorum-sensing-controlled virulence regulatory system. This is a problem, as agr-defective strains are associated with a mortality level in bacteremic infections and a probability of glycopeptide resistance greater than those of other strains. We show here that agr-negative strains have a fitness advantage over agr-positive strains in the presence of sublethal concentrations of some antibiotics and that the fitness defect of agr-positive cells is caused by antibiotic-mediated expression of the agr effector molecule RNAIII. These results offer an explanation of the frequent isolation of agr-defective S. aureus strains in hospitals and will influence how we treat S. aureus infections.
format	article
author	Wilhelm Paulander Anders Nissen Varming Kristoffer T. Bæk Jakob Haaber Dorte Frees Hanne Ingmer
author_facet	Wilhelm Paulander Anders Nissen Varming Kristoffer T. Bæk Jakob Haaber Dorte Frees Hanne Ingmer
author_sort	Wilhelm Paulander
title	Antibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_short	Antibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full	Antibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_fullStr	Antibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_full_unstemmed	Antibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>
title_sort	antibiotic-mediated selection of quorum-sensing-negative <named-content content-type="genus-species">staphylococcus aureus</named-content>
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/7d8517718da2476ba990b27f92366cda
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Antibiotic-Mediated Selection of Quorum-Sensing-Negative <named-content content-type="genus-species">Staphylococcus aureus</named-content>

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