The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections

ABSTRACT Bacterial biofilms are responsible for a variety of serious human infections and are notoriously difficult to treat due to their recalcitrance to antibiotics. Further work is necessary to elicit a full understanding of the mechanism of this antibiotic tolerance. The arginine deiminase (ADI)...

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Autores principales:	Jeffrey A. Freiberg, Yoann Le Breton, Janette M. Harro, Devon L. Allison, Kevin S. McIver, Mark E. Shirtliff
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Streptococcus pyogenes antibiotic tolerance arginine deiminase biofilms group A Streptococcus Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/927df0d4bc884f27a33bf54a25cb23bf
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spelling	oai:doaj.org-article:927df0d4bc884f27a33bf54a25cb23bf2021-11-15T15:56:44ZThe Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections10.1128/mBio.00919-202150-7511https://doaj.org/article/927df0d4bc884f27a33bf54a25cb23bf2020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00919-20https://doaj.org/toc/2150-7511ABSTRACT Bacterial biofilms are responsible for a variety of serious human infections and are notoriously difficult to treat due to their recalcitrance to antibiotics. Further work is necessary to elicit a full understanding of the mechanism of this antibiotic tolerance. The arginine deiminase (ADI) pathway is responsible for bacterial pH maintenance and is highly expressed during biofilm growth in multiple bacterial species. Using the group A Streptococcus (GAS) as a model human pathogen, the ADI pathway was demonstrated to contribute to biofilm growth. The inability of antibiotics to reduce GAS populations when in a biofilm was demonstrated by in vitro studies and a novel animal model of nasopharyngeal infection. However, disruption of the ADI pathway returned GAS biofilms to planktonic levels of antibiotic sensitivity, suggesting the ADI pathway is influential in biofilm-related antibiotic treatment failure and provides a new strategic target for the treatment of biofilm infections in GAS and potentially numerous other bacterial species. IMPORTANCE Biofilm-mediated bacterial infections are a major threat to human health because of their recalcitrance to antibiotic treatment. Through the study of Streptococcus pyogenes, a significant human pathogen that is known to form antibiotic-tolerant biofilms, we demonstrated the role that a bacterial pathway known for responding to acid stress plays in biofilm growth and antibiotic tolerance. This not only provides some insight into antibiotic treatment failure in S. pyogenes infections but also, given the widespread nature of this pathway, provides a potentially broad target for antibiofilm therapies. This discovery has the potential to impact the treatment of many different types of recalcitrant biofilm infections.Jeffrey A. FreibergYoann Le BretonJanette M. HarroDevon L. AllisonKevin S. McIverMark E. ShirtliffAmerican Society for MicrobiologyarticleStreptococcus pyogenesantibiotic tolerancearginine deiminasebiofilmsgroup A StreptococcusMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pyogenes antibiotic tolerance arginine deiminase biofilms group A Streptococcus Microbiology QR1-502
spellingShingle	Streptococcus pyogenes antibiotic tolerance arginine deiminase biofilms group A Streptococcus Microbiology QR1-502 Jeffrey A. Freiberg Yoann Le Breton Janette M. Harro Devon L. Allison Kevin S. McIver Mark E. Shirtliff The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections
description	ABSTRACT Bacterial biofilms are responsible for a variety of serious human infections and are notoriously difficult to treat due to their recalcitrance to antibiotics. Further work is necessary to elicit a full understanding of the mechanism of this antibiotic tolerance. The arginine deiminase (ADI) pathway is responsible for bacterial pH maintenance and is highly expressed during biofilm growth in multiple bacterial species. Using the group A Streptococcus (GAS) as a model human pathogen, the ADI pathway was demonstrated to contribute to biofilm growth. The inability of antibiotics to reduce GAS populations when in a biofilm was demonstrated by in vitro studies and a novel animal model of nasopharyngeal infection. However, disruption of the ADI pathway returned GAS biofilms to planktonic levels of antibiotic sensitivity, suggesting the ADI pathway is influential in biofilm-related antibiotic treatment failure and provides a new strategic target for the treatment of biofilm infections in GAS and potentially numerous other bacterial species. IMPORTANCE Biofilm-mediated bacterial infections are a major threat to human health because of their recalcitrance to antibiotic treatment. Through the study of Streptococcus pyogenes, a significant human pathogen that is known to form antibiotic-tolerant biofilms, we demonstrated the role that a bacterial pathway known for responding to acid stress plays in biofilm growth and antibiotic tolerance. This not only provides some insight into antibiotic treatment failure in S. pyogenes infections but also, given the widespread nature of this pathway, provides a potentially broad target for antibiofilm therapies. This discovery has the potential to impact the treatment of many different types of recalcitrant biofilm infections.
format	article
author	Jeffrey A. Freiberg Yoann Le Breton Janette M. Harro Devon L. Allison Kevin S. McIver Mark E. Shirtliff
author_facet	Jeffrey A. Freiberg Yoann Le Breton Janette M. Harro Devon L. Allison Kevin S. McIver Mark E. Shirtliff
author_sort	Jeffrey A. Freiberg
title	The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections
title_short	The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections
title_full	The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections
title_fullStr	The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections
title_full_unstemmed	The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections
title_sort	arginine deiminase pathway impacts antibiotic tolerance during biofilm-mediated <named-content content-type="genus-species">streptococcus pyogenes</named-content> infections
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/927df0d4bc884f27a33bf54a25cb23bf
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The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Infections

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