Complete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant <named-content content-type="genus-species">Enterococcus faecalis</named-content> V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone
ABSTRACT All enterococci produce a complex polysaccharide called the enterococcal polysaccharide antigen (EPA). This polymer is required for normal cell growth and division and for resistance to cephalosporins and plays a critical role in host-pathogen interaction. The EPA contributes to host coloni...
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American Society for Microbiology
2020
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oai:doaj.org-article:f1771701db934f8daf3dbbae1983d8182021-11-15T15:57:03ZComplete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant <named-content content-type="genus-species">Enterococcus faecalis</named-content> V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone10.1128/mBio.00277-202150-7511https://doaj.org/article/f1771701db934f8daf3dbbae1983d8182020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00277-20https://doaj.org/toc/2150-7511ABSTRACT All enterococci produce a complex polysaccharide called the enterococcal polysaccharide antigen (EPA). This polymer is required for normal cell growth and division and for resistance to cephalosporins and plays a critical role in host-pathogen interaction. The EPA contributes to host colonization and is essential for virulence, conferring resistance to phagocytosis during the infection. Recent studies revealed that the “decorations” of the EPA polymer, encoded by genetic loci that are variable between isolates, underpin the biological activity of this surface polysaccharide. In this work, we investigated the structure of the EPA polymer produced by the high-risk enterococcal clonal complex Enterococcus faecalis V583. We analyzed purified EPA from the wild-type strain and a mutant lacking decorations and elucidated the structure of the EPA backbone and decorations. We showed that the rhamnan backbone of EPA is composed of a hexasaccharide repeat unit of C2- and C3-linked rhamnan chains, partially substituted in the C3 position by α-glucose (α-Glc) and in the C2 position by β-N-acetylglucosamine (β-GlcNAc). The so-called “EPA decorations” consist of phosphopolysaccharide chains corresponding to teichoic acids covalently bound to the rhamnan backbone. The elucidation of the complete EPA structure allowed us to propose a biosynthetic pathway, a first essential step toward the design of antimicrobials targeting the synthesis of this virulence factor. IMPORTANCE Enterococci are opportunistic pathogens responsible for hospital- and community-acquired infections. All enterococci produce a surface polysaccharide called EPA (enterococcal polysaccharide antigen) required for biofilm formation, antibiotic resistance, and pathogenesis. Despite the critical role of EPA in cell growth and division and as a major virulence factor, no information is available on its structure. Here, we report the complete structure of the EPA polymer produced by the model strain E. faecalis V583. We describe the structure of the EPA backbone, made of a rhamnan hexasaccharide substituted by Glc and GlcNAc residues, and show that teichoic acids are covalently bound to this rhamnan chain, forming the so-called “EPA decorations” essential for host colonization and pathogenesis. This report represents a key step in efforts to identify the structural properties of EPA that are essential for its biological activity and to identify novel targets to develop preventive and therapeutic approaches against enterococci.Yann GuerardelIrina SadovskayaEmmanuel MaesSylviane FurlanMarie-Pierre Chapot-ChartierStéphane MesnageLionel Rigottier-GoisPascale SerrorAmerican Society for MicrobiologyarticleE. faecalisteichoic acidscell wall polysaccharideenterococcal polysaccharide antigenEnterococcus faecalisrhamnanMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
E. faecalis teichoic acids cell wall polysaccharide enterococcal polysaccharide antigen Enterococcus faecalis rhamnan Microbiology QR1-502 |
| spellingShingle |
E. faecalis teichoic acids cell wall polysaccharide enterococcal polysaccharide antigen Enterococcus faecalis rhamnan Microbiology QR1-502 Yann Guerardel Irina Sadovskaya Emmanuel Maes Sylviane Furlan Marie-Pierre Chapot-Chartier Stéphane Mesnage Lionel Rigottier-Gois Pascale Serror Complete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant <named-content content-type="genus-species">Enterococcus faecalis</named-content> V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone |
| description |
ABSTRACT All enterococci produce a complex polysaccharide called the enterococcal polysaccharide antigen (EPA). This polymer is required for normal cell growth and division and for resistance to cephalosporins and plays a critical role in host-pathogen interaction. The EPA contributes to host colonization and is essential for virulence, conferring resistance to phagocytosis during the infection. Recent studies revealed that the “decorations” of the EPA polymer, encoded by genetic loci that are variable between isolates, underpin the biological activity of this surface polysaccharide. In this work, we investigated the structure of the EPA polymer produced by the high-risk enterococcal clonal complex Enterococcus faecalis V583. We analyzed purified EPA from the wild-type strain and a mutant lacking decorations and elucidated the structure of the EPA backbone and decorations. We showed that the rhamnan backbone of EPA is composed of a hexasaccharide repeat unit of C2- and C3-linked rhamnan chains, partially substituted in the C3 position by α-glucose (α-Glc) and in the C2 position by β-N-acetylglucosamine (β-GlcNAc). The so-called “EPA decorations” consist of phosphopolysaccharide chains corresponding to teichoic acids covalently bound to the rhamnan backbone. The elucidation of the complete EPA structure allowed us to propose a biosynthetic pathway, a first essential step toward the design of antimicrobials targeting the synthesis of this virulence factor. IMPORTANCE Enterococci are opportunistic pathogens responsible for hospital- and community-acquired infections. All enterococci produce a surface polysaccharide called EPA (enterococcal polysaccharide antigen) required for biofilm formation, antibiotic resistance, and pathogenesis. Despite the critical role of EPA in cell growth and division and as a major virulence factor, no information is available on its structure. Here, we report the complete structure of the EPA polymer produced by the model strain E. faecalis V583. We describe the structure of the EPA backbone, made of a rhamnan hexasaccharide substituted by Glc and GlcNAc residues, and show that teichoic acids are covalently bound to this rhamnan chain, forming the so-called “EPA decorations” essential for host colonization and pathogenesis. This report represents a key step in efforts to identify the structural properties of EPA that are essential for its biological activity and to identify novel targets to develop preventive and therapeutic approaches against enterococci. |
| format |
article |
| author |
Yann Guerardel Irina Sadovskaya Emmanuel Maes Sylviane Furlan Marie-Pierre Chapot-Chartier Stéphane Mesnage Lionel Rigottier-Gois Pascale Serror |
| author_facet |
Yann Guerardel Irina Sadovskaya Emmanuel Maes Sylviane Furlan Marie-Pierre Chapot-Chartier Stéphane Mesnage Lionel Rigottier-Gois Pascale Serror |
| author_sort |
Yann Guerardel |
| title |
Complete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant <named-content content-type="genus-species">Enterococcus faecalis</named-content> V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone |
| title_short |
Complete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant <named-content content-type="genus-species">Enterococcus faecalis</named-content> V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone |
| title_full |
Complete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant <named-content content-type="genus-species">Enterococcus faecalis</named-content> V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone |
| title_fullStr |
Complete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant <named-content content-type="genus-species">Enterococcus faecalis</named-content> V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone |
| title_full_unstemmed |
Complete Structure of the Enterococcal Polysaccharide Antigen (EPA) of Vancomycin-Resistant <named-content content-type="genus-species">Enterococcus faecalis</named-content> V583 Reveals that EPA Decorations Are Teichoic Acids Covalently Linked to a Rhamnopolysaccharide Backbone |
| title_sort |
complete structure of the enterococcal polysaccharide antigen (epa) of vancomycin-resistant <named-content content-type="genus-species">enterococcus faecalis</named-content> v583 reveals that epa decorations are teichoic acids covalently linked to a rhamnopolysaccharide backbone |
| publisher |
American Society for Microbiology |
| publishDate |
2020 |
| url |
https://doaj.org/article/f1771701db934f8daf3dbbae1983d818 |
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