<italic toggle="yes">Pseudomonas aeruginosa</italic> Alters <italic toggle="yes">Staphylococcus aureus</italic> Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection

ABSTRACT The airways of cystic fibrosis (CF) patients have thick mucus, which fosters chronic, polymicrobial infections. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients. In this study, we tested whether P. aeruginosa influences the...

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Autores principales: Giulia Orazi, George A. O’Toole
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Publicado: American Society for Microbiology 2017
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spelling oai:doaj.org-article:63a92ba9f86e4358a9da392abf288b6d2021-11-15T15:51:44Z<italic toggle="yes">Pseudomonas aeruginosa</italic> Alters <italic toggle="yes">Staphylococcus aureus</italic> Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection10.1128/mBio.00873-172150-7511https://doaj.org/article/63a92ba9f86e4358a9da392abf288b6d2017-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00873-17https://doaj.org/toc/2150-7511ABSTRACT The airways of cystic fibrosis (CF) patients have thick mucus, which fosters chronic, polymicrobial infections. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients. In this study, we tested whether P. aeruginosa influences the susceptibility of S. aureus to frontline antibiotics used to treat CF lung infections. Using our in vitro coculture model, we observed that addition of P. aeruginosa supernatants to S. aureus biofilms grown either on epithelial cells or on plastic significantly decreased the susceptibility of S. aureus to vancomycin. Mutant analyses showed that 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), a component of the P. aeruginosa Pseudomonas quinolone signal (PQS) system, protects S. aureus from the antimicrobial activity of vancomycin. Similarly, the siderophores pyoverdine and pyochelin also contribute to the ability of P. aeruginosa to protect S. aureus from vancomycin, as did growth under anoxia. Under our experimental conditions, HQNO, P. aeruginosa supernatant, and growth under anoxia decreased S. aureus growth, likely explaining why this cell wall-targeting antibiotic is less effective. P. aeruginosa supernatant did not confer additional protection to slow-growing S. aureus small colony variants. Importantly, P. aeruginosa supernatant protects S. aureus from other inhibitors of cell wall synthesis as well as protein synthesis-targeting antibiotics in an HQNO- and siderophore-dependent manner. We propose a model whereby P. aeruginosa causes S. aureus to shift to fermentative growth when these organisms are grown in coculture, leading to reduction in S. aureus growth and decreased susceptibility to antibiotics targeting cell wall and protein synthesis. IMPORTANCE Cystic fibrosis (CF) lung infections are chronic and difficult to eradicate. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients and are associated with poor patient outcomes. Both organisms adopt a biofilm mode of growth, which contributes to high tolerance to antibiotic treatment and the recalcitrant nature of these infections. Here, we show that P. aeruginosa exoproducts decrease the sensitivity of S. aureus biofilm and planktonic populations to vancomycin, a frontline antibiotic used to treat methicillin-resistant S. aureus in CF patients. P. aeruginosa also protects S. aureus from other cell wall-active antibiotics as well as various classes of protein synthesis inhibitors. Thus, interspecies interactions can have dramatic and unexpected consequences on antibiotic sensitivity. This study underscores the potential impact of interspecies interactions on antibiotic efficacy in the context of complex, polymicrobial infections.Giulia OraziGeorge A. O’TooleAmerican Society for MicrobiologyarticlePseudomonasStaphylococcus aureusantibiotic tolerancebiofilmscystic fibrosispolymicrobialMicrobiologyQR1-502ENmBio, Vol 8, Iss 4 (2017)
institution DOAJ
collection DOAJ
language EN
topic Pseudomonas
Staphylococcus aureus
antibiotic tolerance
biofilms
cystic fibrosis
polymicrobial
Microbiology
QR1-502
spellingShingle Pseudomonas
Staphylococcus aureus
antibiotic tolerance
biofilms
cystic fibrosis
polymicrobial
Microbiology
QR1-502
Giulia Orazi
George A. O’Toole
<italic toggle="yes">Pseudomonas aeruginosa</italic> Alters <italic toggle="yes">Staphylococcus aureus</italic> Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection
description ABSTRACT The airways of cystic fibrosis (CF) patients have thick mucus, which fosters chronic, polymicrobial infections. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients. In this study, we tested whether P. aeruginosa influences the susceptibility of S. aureus to frontline antibiotics used to treat CF lung infections. Using our in vitro coculture model, we observed that addition of P. aeruginosa supernatants to S. aureus biofilms grown either on epithelial cells or on plastic significantly decreased the susceptibility of S. aureus to vancomycin. Mutant analyses showed that 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO), a component of the P. aeruginosa Pseudomonas quinolone signal (PQS) system, protects S. aureus from the antimicrobial activity of vancomycin. Similarly, the siderophores pyoverdine and pyochelin also contribute to the ability of P. aeruginosa to protect S. aureus from vancomycin, as did growth under anoxia. Under our experimental conditions, HQNO, P. aeruginosa supernatant, and growth under anoxia decreased S. aureus growth, likely explaining why this cell wall-targeting antibiotic is less effective. P. aeruginosa supernatant did not confer additional protection to slow-growing S. aureus small colony variants. Importantly, P. aeruginosa supernatant protects S. aureus from other inhibitors of cell wall synthesis as well as protein synthesis-targeting antibiotics in an HQNO- and siderophore-dependent manner. We propose a model whereby P. aeruginosa causes S. aureus to shift to fermentative growth when these organisms are grown in coculture, leading to reduction in S. aureus growth and decreased susceptibility to antibiotics targeting cell wall and protein synthesis. IMPORTANCE Cystic fibrosis (CF) lung infections are chronic and difficult to eradicate. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most prevalent respiratory pathogens in CF patients and are associated with poor patient outcomes. Both organisms adopt a biofilm mode of growth, which contributes to high tolerance to antibiotic treatment and the recalcitrant nature of these infections. Here, we show that P. aeruginosa exoproducts decrease the sensitivity of S. aureus biofilm and planktonic populations to vancomycin, a frontline antibiotic used to treat methicillin-resistant S. aureus in CF patients. P. aeruginosa also protects S. aureus from other cell wall-active antibiotics as well as various classes of protein synthesis inhibitors. Thus, interspecies interactions can have dramatic and unexpected consequences on antibiotic sensitivity. This study underscores the potential impact of interspecies interactions on antibiotic efficacy in the context of complex, polymicrobial infections.
format article
author Giulia Orazi
George A. O’Toole
author_facet Giulia Orazi
George A. O’Toole
author_sort Giulia Orazi
title <italic toggle="yes">Pseudomonas aeruginosa</italic> Alters <italic toggle="yes">Staphylococcus aureus</italic> Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection
title_short <italic toggle="yes">Pseudomonas aeruginosa</italic> Alters <italic toggle="yes">Staphylococcus aureus</italic> Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection
title_full <italic toggle="yes">Pseudomonas aeruginosa</italic> Alters <italic toggle="yes">Staphylococcus aureus</italic> Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection
title_fullStr <italic toggle="yes">Pseudomonas aeruginosa</italic> Alters <italic toggle="yes">Staphylococcus aureus</italic> Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection
title_full_unstemmed <italic toggle="yes">Pseudomonas aeruginosa</italic> Alters <italic toggle="yes">Staphylococcus aureus</italic> Sensitivity to Vancomycin in a Biofilm Model of Cystic Fibrosis Infection
title_sort <italic toggle="yes">pseudomonas aeruginosa</italic> alters <italic toggle="yes">staphylococcus aureus</italic> sensitivity to vancomycin in a biofilm model of cystic fibrosis infection
publisher American Society for Microbiology
publishDate 2017
url https://doaj.org/article/63a92ba9f86e4358a9da392abf288b6d
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AT georgeaotoole italictoggleyespseudomonasaeruginosaitalicaltersitalictoggleyesstaphylococcusaureusitalicsensitivitytovancomycininabiofilmmodelofcysticfibrosisinfection
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