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)...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-08-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00919-20 |
| _version_ | 1818406298815823872 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T09:09:43Z |
| format | Article |
| id | doaj.art-927df0d4bc884f27a33bf54a25cb23bf |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T09:09:43Z |
| publishDate | 2020-08-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-927df0d4bc884f27a33bf54a25cb23bf2022-12-21T23:08:35ZengAmerican Society for MicrobiologymBio2150-75112020-08-0111410.1128/mBio.00919-20The Arginine Deiminase Pathway Impacts Antibiotic Tolerance during Biofilm-Mediated <named-content content-type="genus-species">Streptococcus pyogenes</named-content> InfectionsJeffrey A. Freiberg0Yoann Le Breton1Janette M. Harro2Devon L. Allison3Kevin S. McIver4Mark E. Shirtliff5Department of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USADepartment of Cell Biology & Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, USADepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USADepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USADepartment of Cell Biology & Molecular Genetics and Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, USADepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, Maryland, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.00919-20Streptococcus pyogenesantibiotic tolerancearginine deiminasebiofilmsgroup A Streptococcus |
| spellingShingle | 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 mBio Streptococcus pyogenes antibiotic tolerance arginine deiminase biofilms group A Streptococcus |
| title | 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_short | 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 |
| topic | Streptococcus pyogenes antibiotic tolerance arginine deiminase biofilms group A Streptococcus |
| url | https://journals.asm.org/doi/10.1128/mBio.00919-20 |
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