Enterococcal cell wall remodelling underpins pathogenesis via the release of the Enteroccocal Polysaccharide Antigen (EPA).
| Title: | Enterococcal cell wall remodelling underpins pathogenesis via the release of the Enteroccocal Polysaccharide Antigen (EPA). |
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| Authors: | Smith RE; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Michno BJ; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków, Poland.; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Krakow, Poland.; Christena RL; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; O'Dea F; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Davis JL; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Lidbury IDEA; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Alamán-Zárate MG; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Stefanidi D; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Maes E; University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.; Fisher H; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom.; Prajsnar TK; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków, Poland.; Mesnage S; Molecular Microbiology, School of Biosciences, University of Sheffield, Sheffield, United Kingdom. |
| Source: | PLoS pathogens [PLoS Pathog] 2025 Jun 23; Vol. 21 (6), pp. e1012771. Date of Electronic Publication: 2025 Jun 23 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science, c2005- |
| MeSH Terms: | Cell Wall*/metabolism ; Cell Wall*/immunology ; Enterococcus faecalis*/pathogenicity ; Enterococcus faecalis*/immunology ; Enterococcus faecalis*/metabolism ; Gram-Positive Bacterial Infections*/immunology ; Gram-Positive Bacterial Infections*/microbiology ; Gram-Positive Bacterial Infections*/pathology ; Polysaccharides, Bacterial*/metabolism ; Polysaccharides, Bacterial*/immunology ; Antigens, Bacterial*/metabolism ; Antigens, Bacterial*/immunology; Bacterial Proteins/metabolism ; Bacterial Proteins/genetics ; Virulence ; Animals ; Mice ; Humans |
| Abstract: | Enterococci are opportunistic pathogens displaying a characteristic ovoid shape, typically forming pairs of cells (diplococci) and short chains. Control of cell chain length in Enterococcus faecalis relies on the activity of the major N-acetylglucosaminidase AtlA. The formation of short chains and diplococci is critical during pathogenesis for dissemination in the host and to limit recognition by innate immune effectors such as complement molecules and phagocytes. Here, we identify AtlE, an N-acetylmuramidase that contributes to septum cleavage during stationary phase in the absence of AtlA. AtlE is encoded by the locus required to produce the decoration subunits of the Enterococcal Polysaccharide Antigen (EPA), which mediate evasion of phagocytosis. We show that peptidoglycan hydrolysis by AtlE is essential for pathogenesis and demonstrate that soluble cell wall fragments containing EPA decorations increase the virulence of E. faecalis, suggesting that EPA plays a role as a decoy molecule to evade host defences. This research sheds light on the complex interplay between bacterial cell division, cell wall remodelling, and the host immune system, providing valuable insights into a novel mechanism underlying the virulence of E. faecalis.; (Copyright: © 2025 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
| Competing Interests: | The authors have no competing interests to declare. |
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| Substance Nomenclature: | 0 (Polysaccharides, Bacterial); 0 (Antigens, Bacterial); 0 (Bacterial Proteins) |
| Entry Date(s): | Date Created: 20250623 Date Completed: 20250630 Latest Revision: 20250702 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12208459 |
| DOI: | 10.1371/journal.ppat.1012771 |
| PMID: | 40549821 |
| Database: | MEDLINE |
Journal Article