Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation

ABSTRACT Staphylococcus aureus is a leading cause of catheter-related bloodstream infections. Biofilms form on these implants and are held together by a matrix composed of proteins, polysaccharides, and extracellular DNA (eDNA). Heparin is a sulfated glycosaminoglycan that is routinely used in centr...

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Autores principales:	Surabhi Mishra, Alexander R. Horswill
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	heparin Staphylococcus aureus biofilm eDNA glycosaminoglycan MRSA Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ad88d31f12e94b5b94ef04223697329c
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spelling	oai:doaj.org-article:ad88d31f12e94b5b94ef04223697329c2021-11-15T15:21:46ZHeparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation10.1128/mSphere.00135-172379-5042https://doaj.org/article/ad88d31f12e94b5b94ef04223697329c2017-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00135-17https://doaj.org/toc/2379-5042ABSTRACT Staphylococcus aureus is a leading cause of catheter-related bloodstream infections. Biofilms form on these implants and are held together by a matrix composed of proteins, polysaccharides, and extracellular DNA (eDNA). Heparin is a sulfated glycosaminoglycan that is routinely used in central venous catheters to prevent thrombosis, but it has been shown to stimulate S. aureus biofilm formation through an unknown mechanism. Data presented here reveal that heparin enhances biofilm capacity in many S. aureus and coagulase-negative staphylococcal strains, and it is incorporated into the USA300 methicillin-resistant S. aureus (MRSA) biofilm matrix. The S. aureus USA300 biofilms containing heparin are sensitive to proteinase K treatment, which suggests that proteins have an important structural role during heparin incorporation. Multiple heparin-binding proteins were identified by proteomics of the secreted and cell wall fractions. Proteins known to contribute to biofilm were identified, and some proteins were reported to have the ability to bind eDNA, such as the major autolysin (Atl) and the immunodominant surface protein B (IsaB). Mutants defective in IsaB showed a moderate decrease in biofilm capacity in the presence of heparin. Our findings suggested that heparin is substituting for eDNA during S. aureus biofilm development. To test this model, eDNA content was increased in biofilms through inactivation of nuclease activity, and the heparin enhancement effect was attenuated. Collectively, these data support the hypothesis that S. aureus can incorporate heparin into the matrix and enhance biofilm capacity by taking advantage of existing eDNA-binding proteins. IMPORTANCE Staphylococcus aureus and coagulase-negative staphylococci (CoNS) are the leading causes of catheter implant infections. Identifying the factors that stimulate catheter infection and the mechanism involved is important for preventing such infections. Heparin, the main component of catheter lock solutions, has been shown previously to stimulate S. aureus biofilm formation through an unknown pathway. This work identifies multiple heparin-binding proteins in S. aureus, and it reveals a potential mechanism through which heparin enhances biofilm capacity. Understanding the details of the heparin enhancement effect could guide future use of appropriate lock solutions for catheter implants.Surabhi MishraAlexander R. HorswillAmerican Society for MicrobiologyarticleheparinStaphylococcus aureusbiofilmeDNAglycosaminoglycanMRSAMicrobiologyQR1-502ENmSphere, Vol 2, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	heparin Staphylococcus aureus biofilm eDNA glycosaminoglycan MRSA Microbiology QR1-502
spellingShingle	heparin Staphylococcus aureus biofilm eDNA glycosaminoglycan MRSA Microbiology QR1-502 Surabhi Mishra Alexander R. Horswill Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation
description	ABSTRACT Staphylococcus aureus is a leading cause of catheter-related bloodstream infections. Biofilms form on these implants and are held together by a matrix composed of proteins, polysaccharides, and extracellular DNA (eDNA). Heparin is a sulfated glycosaminoglycan that is routinely used in central venous catheters to prevent thrombosis, but it has been shown to stimulate S. aureus biofilm formation through an unknown mechanism. Data presented here reveal that heparin enhances biofilm capacity in many S. aureus and coagulase-negative staphylococcal strains, and it is incorporated into the USA300 methicillin-resistant S. aureus (MRSA) biofilm matrix. The S. aureus USA300 biofilms containing heparin are sensitive to proteinase K treatment, which suggests that proteins have an important structural role during heparin incorporation. Multiple heparin-binding proteins were identified by proteomics of the secreted and cell wall fractions. Proteins known to contribute to biofilm were identified, and some proteins were reported to have the ability to bind eDNA, such as the major autolysin (Atl) and the immunodominant surface protein B (IsaB). Mutants defective in IsaB showed a moderate decrease in biofilm capacity in the presence of heparin. Our findings suggested that heparin is substituting for eDNA during S. aureus biofilm development. To test this model, eDNA content was increased in biofilms through inactivation of nuclease activity, and the heparin enhancement effect was attenuated. Collectively, these data support the hypothesis that S. aureus can incorporate heparin into the matrix and enhance biofilm capacity by taking advantage of existing eDNA-binding proteins. IMPORTANCE Staphylococcus aureus and coagulase-negative staphylococci (CoNS) are the leading causes of catheter implant infections. Identifying the factors that stimulate catheter infection and the mechanism involved is important for preventing such infections. Heparin, the main component of catheter lock solutions, has been shown previously to stimulate S. aureus biofilm formation through an unknown pathway. This work identifies multiple heparin-binding proteins in S. aureus, and it reveals a potential mechanism through which heparin enhances biofilm capacity. Understanding the details of the heparin enhancement effect could guide future use of appropriate lock solutions for catheter implants.
format	article
author	Surabhi Mishra Alexander R. Horswill
author_facet	Surabhi Mishra Alexander R. Horswill
author_sort	Surabhi Mishra
title	Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation
title_short	Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation
title_full	Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation
title_fullStr	Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation
title_full_unstemmed	Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation
title_sort	heparin mimics extracellular dna in binding to cell surface-localized proteins and promoting <named-content content-type="genus-species">staphylococcus aureus</named-content> biofilm formation
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/ad88d31f12e94b5b94ef04223697329c
work_keys_str_mv	AT surabhimishra heparinmimicsextracellulardnainbindingtocellsurfacelocalizedproteinsandpromotingnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentbiofilmformation AT alexanderrhorswill heparinmimicsextracellulardnainbindingtocellsurfacelocalizedproteinsandpromotingnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentbiofilmformation
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Heparin Mimics Extracellular DNA in Binding to Cell Surface-Localized Proteins and Promoting <named-content content-type="genus-species">Staphylococcus aureus</named-content> Biofilm Formation

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