<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics

ABSTRACT Pseudomonas aeruginosa and Staphylococcus aureus often cause chronic, recalcitrant infections in large part due to their ability to form biofilms. The biofilm mode of growth enables these organisms to withstand antibacterial insults that would effectively eliminate their planktonic counterp...

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Autores principales:	Giulia Orazi, Kathryn L. Ruoff, George A. O’Toole
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Pseudomonas aeruginosa Staphylococcus aureus antibiotics biofilm membrane Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b7e88a063ef7491497001fdb38f12c12
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spelling	oai:doaj.org-article:b7e88a063ef7491497001fdb38f12c122021-11-15T16:22:10Z<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics10.1128/mBio.01501-192150-7511https://doaj.org/article/b7e88a063ef7491497001fdb38f12c122019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01501-19https://doaj.org/toc/2150-7511ABSTRACT Pseudomonas aeruginosa and Staphylococcus aureus often cause chronic, recalcitrant infections in large part due to their ability to form biofilms. The biofilm mode of growth enables these organisms to withstand antibacterial insults that would effectively eliminate their planktonic counterparts. We found that P. aeruginosa supernatant increased the sensitivity of S. aureus biofilms to multiple antimicrobial compounds, including fluoroquinolones and membrane-targeting antibacterial agents, including the antiseptic chloroxylenol. Treatment of S. aureus with the antiseptic chloroxylenol alone did not decrease biofilm cell viability; however, the combination of chloroxylenol and P. aeruginosa supernatant led to a 4-log reduction in S. aureus biofilm viability compared to exposure to chloroxylenol alone. We found that the P. aeruginosa-produced small molecule 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO) is responsible for the observed heightened sensitivity of S. aureus to chloroxylenol. Similarly, HQNO increased the susceptibility of S. aureus biofilms to other compounds, including both traditional and nontraditional antibiotics, which permeabilize bacterial membranes. Genetic and phenotypic studies support a model whereby HQNO causes an increase in S. aureus membrane fluidity, thereby improving the efficacy of membrane-targeting antiseptics and antibiotics. Importantly, our data show that P. aeruginosa exoproducts can enhance the ability of various antimicrobial agents to kill biofilm populations of S. aureus that are typically difficult to eradicate. Finally, our discovery that altering membrane fluidity shifts antimicrobial sensitivity profiles of bacterial biofilms may guide new approaches to target persistent infections, such as those commonly found in respiratory tract infections and in chronic wounds. IMPORTANCE The thick mucus in the airways of cystic fibrosis (CF) patients predisposes them to frequent, polymicrobial respiratory infections. Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from the airways of individuals with CF, as well as from diabetic foot ulcers and other wounds. Both organisms form biofilms, which are notoriously difficult to eradicate and promote chronic infection. In this study, we have shown that P. aeruginosa-secreted factors can increase the efficacy of compounds that alone have little or no bactericidal activity against S. aureus biofilms. In particular, we discovered that P. aeruginosa exoproducts can potentiate the antistaphylococcal activity of phenol-based antiseptics and other membrane-active drugs. Our findings illustrate that polymicrobial interactions can dramatically increase antibacterial efficacy in vitro and suggest that altering membrane physiology promotes the ability of certain drugs to kill bacterial biofilms—knowledge that may provide a path for the discovery of new biofilm-targeting antimicrobial strategies.Giulia OraziKathryn L. RuoffGeorge A. O’TooleAmerican Society for MicrobiologyarticlePseudomonas aeruginosaStaphylococcus aureusantibioticsbiofilmmembraneMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pseudomonas aeruginosa Staphylococcus aureus antibiotics biofilm membrane Microbiology QR1-502
spellingShingle	Pseudomonas aeruginosa Staphylococcus aureus antibiotics biofilm membrane Microbiology QR1-502 Giulia Orazi Kathryn L. Ruoff George A. O’Toole <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics
description	ABSTRACT Pseudomonas aeruginosa and Staphylococcus aureus often cause chronic, recalcitrant infections in large part due to their ability to form biofilms. The biofilm mode of growth enables these organisms to withstand antibacterial insults that would effectively eliminate their planktonic counterparts. We found that P. aeruginosa supernatant increased the sensitivity of S. aureus biofilms to multiple antimicrobial compounds, including fluoroquinolones and membrane-targeting antibacterial agents, including the antiseptic chloroxylenol. Treatment of S. aureus with the antiseptic chloroxylenol alone did not decrease biofilm cell viability; however, the combination of chloroxylenol and P. aeruginosa supernatant led to a 4-log reduction in S. aureus biofilm viability compared to exposure to chloroxylenol alone. We found that the P. aeruginosa-produced small molecule 2-n-heptyl-4-hydroxyquinoline N-oxide (HQNO) is responsible for the observed heightened sensitivity of S. aureus to chloroxylenol. Similarly, HQNO increased the susceptibility of S. aureus biofilms to other compounds, including both traditional and nontraditional antibiotics, which permeabilize bacterial membranes. Genetic and phenotypic studies support a model whereby HQNO causes an increase in S. aureus membrane fluidity, thereby improving the efficacy of membrane-targeting antiseptics and antibiotics. Importantly, our data show that P. aeruginosa exoproducts can enhance the ability of various antimicrobial agents to kill biofilm populations of S. aureus that are typically difficult to eradicate. Finally, our discovery that altering membrane fluidity shifts antimicrobial sensitivity profiles of bacterial biofilms may guide new approaches to target persistent infections, such as those commonly found in respiratory tract infections and in chronic wounds. IMPORTANCE The thick mucus in the airways of cystic fibrosis (CF) patients predisposes them to frequent, polymicrobial respiratory infections. Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from the airways of individuals with CF, as well as from diabetic foot ulcers and other wounds. Both organisms form biofilms, which are notoriously difficult to eradicate and promote chronic infection. In this study, we have shown that P. aeruginosa-secreted factors can increase the efficacy of compounds that alone have little or no bactericidal activity against S. aureus biofilms. In particular, we discovered that P. aeruginosa exoproducts can potentiate the antistaphylococcal activity of phenol-based antiseptics and other membrane-active drugs. Our findings illustrate that polymicrobial interactions can dramatically increase antibacterial efficacy in vitro and suggest that altering membrane physiology promotes the ability of certain drugs to kill bacterial biofilms—knowledge that may provide a path for the discovery of new biofilm-targeting antimicrobial strategies.
format	article
author	Giulia Orazi Kathryn L. Ruoff George A. O’Toole
author_facet	Giulia Orazi Kathryn L. Ruoff George A. O’Toole
author_sort	Giulia Orazi
title	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics
title_short	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics
title_full	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics
title_fullStr	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics
title_full_unstemmed	<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics
title_sort	<named-content content-type="genus-species">pseudomonas aeruginosa</named-content> increases the sensitivity of biofilm-grown <named-content content-type="genus-species">staphylococcus aureus</named-content> to membrane-targeting antiseptics and antibiotics
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/b7e88a063ef7491497001fdb38f12c12
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<named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Increases the Sensitivity of Biofilm-Grown <named-content content-type="genus-species">Staphylococcus aureus</named-content> to Membrane-Targeting Antiseptics and Antibiotics

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