Cited by 10Biochemical and Structural CharacterizationBacterial Genetics and BiotechnologyEscherichia coli research studies

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Structural foundation for the role of enterococcal PrgB in conjugation, biofilm formation, and virulence

Open access

Published version of a preprint

Abstract

Type 4 Secretion Systems are a main driver for the spread of antibiotic resistance genes and virulence factors in bacteria. In Gram-positives, these secretion systems often rely on surface adhesins to enhance cellular aggregation and mating-pair formation. One of the best studied adhesins is PrgB from the conjugative plasmid pCF10 of Enterococcus faecalis , which has been shown to play major roles in conjugation, biofilm formation, and importantly also in bacterial virulence. Since prgB orthologs exist on a large number of conjugative plasmids in various different species, this makes PrgB a model protein for this widespread virulence factor. After characterizing the polymer adhesin domain of PrgB previously, we here report the structure for almost the entire remainder of PrgB, which reveals that PrgB contains four immunoglobulin (Ig)-like domains. Based on this new insight, we re-evaluate previously studied variants and present new in vivo data where specific domains or conserved residues have been removed. For the first time, we can show a decoupling of cellular aggregation from biofilm formation and conjugation in prgB mutant phenotypes. Based on the presented data, we propose a new functional model to explain how PrgB mediates its different functions. We hypothesize that the Ig-like domains act as a rigid stalk that presents the polymer adhesin domain at the right distance from the cell wall.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.7554/elife.84427.3

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 62

  1. Adams, 2002, PHENIX: building new software for automated crystallographic structure determination, Acta Crystallographica. Section D, Biological Crystallography, 58, 1948, 10.1107/s0907444902016657 · DOI · Paper page
  2. Bae, 2002, Two targets in pCF10 DNA for PrgX binding: their role in production of Qa and prgX mRNA and in regulation of pheromone-inducible conjugation, Journal of Molecular Biology, 315, 995, 10.1006/jmbi.2001.5294 · DOI
  3. Bhatty, 2015, Enterococcus faecalis pCF10-encoded surface proteins PrgA, PrgB (aggregation substance) and PrgC contribute to plasmid transfer, biofilm formation and virulence, Molecular Microbiology, 95, 660, 10.1111/mmi.12893 · DOI
  4. Brady, 2010, The changing faces of Streptococcus antigen I/II polypeptide family adhesins, Molecular Microbiology, 77, 276, 10.1111/j.1365-2958.2010.07212.x · DOI
  5. Cabezón, 2015, Towards an integrated model of bacterial conjugation, FEMS Microbiology Reviews, 39, 81, 10.1111/1574-6976.12085 · DOI
  6. Chandler, 2005, A paracrine peptide sex pheromone also acts as an autocrine signal to induce plasmid transfer and virulence factor expression in vivo, PNAS, 102, 15617, 10.1073/pnas.0505545102 · DOI
  7. Chen, 2007, Specificity determinants of conjugative DNA processing in the Enterococcus faecalis plasmid pCF10 and the Lactococcus lactis plasmid pRS01, Molecular Microbiology, 63, 1549, 10.1111/j.1365-2958.2007.05610.x · DOI
  8. Chen, 2008, Enterococcus faecalis PcfC, a spatially localized substrate receptor for Type IV secretion of the pCF10 transfer intermediate, Journal of Bacteriology, 190, 3632, 10.1128/JB.01999-07 · DOI
  9. Chen, 2010, MolProbity: all-atom structure validation for macromolecular crystallography, Acta Crystallographica. Section D, Biological Crystallography, 66, 12, 10.1107/S0907444909042073 · DOI · Paper page
  10. Christie, 1988, Cloning and expression of genes encoding pheromone-inducible antigens of Enterococcus (Streptococcus) faecalis, Journal of Bacteriology, 170, 5161, 10.1128/jb.170.11.5161-5168.1988 · DOI
  11. Chuang, 2009, Multiple functional domains of Enterococcus faecalis aggregation substance Asc10 contribute to endocarditis virulence, Infection and Immunity, 77, 539, 10.1128/IAI.01034-08 · DOI
  12. Chuang-Smith, 2010, Acceleration of Enterococcus faecalis biofilm formation by aggregation substance expression in an ex vivo model of cardiac valve colonization, PLOS ONE, 5, 10.1371/journal.pone.0015798 · DOI
  13. Daep, 2011, Structural dissection and in vivo effectiveness of a peptide inhibitor of Porphyromonas gingivalis adherence to Streptococcus gordonii, Infection and Immunity, 79, 67, 10.1128/IAI.00361-10 · DOI
  14. Dunny, 2013, Enterococcal sex pheromones: signaling, social behavior, and evolution, Annual Review of Genetics, 47, 457, 10.1146/annurev-genet-111212-133449 · DOI
  15. Dunny, 2016, Enterococcal sex pheromones: Evolutionary pathways to complex, two-signal systems, Journal of Bacteriology, 198, 1556, 10.1128/JB.00128-16 · DOI
  16. Emsley, 2010, Features and development of Coot, Acta Crystallographica. Section D, Biological Crystallography, 66, 486, 10.1107/S0907444910007493 · DOI · Paper page
  17. Forsgren, 2009, Crystal structure of the variable domain of the Streptococcus gordonii surface protein SspB, Protein Science, 18, 1896, 10.1002/pro.200 · DOI
  18. Forsgren, 2010, Two intramolecular isopeptide bonds are identified in the crystal structure of the Streptococcus gordonii SspB C-terminal domain, Journal of Molecular Biology, 397, 740, 10.1016/j.jmb.2010.01.065 · DOI
  19. Franklin, 2013, The AgI/II family adhesin AspA is required for respiratory infection by Streptococcus pyogenes, PLOS ONE, 8, 10.1371/journal.pone.0062433 · DOI
  20. Galli, 1992, Transcriptional control of sex-pheromone-inducible genes on plasmid pAD1 of Enterococcus faecalis and sequence analysis of a third structural gene for (pPD1-encoded) aggregation substance, Molecular Microbiology, 6, 1297, 10.1111/j.1365-2958.1992.tb00851.x · DOI
  21. Geertsma, 2011, A versatile and efficient high-throughput cloning tool for structural biology, Biochemistry, 50, 3272, 10.1021/bi200178z · DOI
  22. Gilmore, 2013, Genomic transition of enterococci from gut commensals to leading causes of multidrug-resistant hospital infection in the antibiotic era, Current Opinion in Microbiology, 16, 10, 10.1016/j.mib.2013.01.006 · DOI
  23. Grohmann, 2018, Type IV secretion in Gram-negative and Gram-positive bacteria, Molecular Microbiology, 107, 455, 10.1111/mmi.13896 · DOI
  24. Halaby, 1998, The immunoglobulin superfamily: an insight on its tissular, species, and functional diversity, Journal of Molecular Evolution, 46, 389, 10.1007/pl00006318 · DOI
  25. Hall, 2014, Structure of the C-terminal domain of AspA (antigen I/II-family) protein from Streptococcus pyogenes, FEBS Open Bio, 4, 283, 10.1016/j.fob.2014.02.012 · DOI
  26. Hidron, 2008, NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007, Infection Control and Hospital Epidemiology, 29, 996, 10.1086/591861 · DOI · Paper page
  27. Hirt, 2005, Characterization of the Pheromone Response of the Enterococcus faecalis Conjugative Plasmid pCF10: Complete Sequence and Comparative Analysis of the Transcriptional and Phenotypic Responses of pCF10-Containing Cells to Pheromone Induction, Journal of Bacteriology, 187, 1044, 10.1128/JB.187.3.1044-1054.2005 · DOI
  28. Hirt, 2022, Dynamics of plasmid-mediated niche invasion, immunity to invasion, and pheromone-inducible conjugation in the murine gastrointestinal tract, Nature Communications, 13, 10.1038/s41467-022-29028-7 · DOI
  29. Holm, 2020, DALI and the persistence of protein shape, Protein Science, 29, 128, 10.1002/pro.3749 · DOI
  30. Järvå, 2020, Polymer adhesin domains in gram-positive cell surface proteins, Frontiers in Microbiology, 11, 10.3389/fmicb.2020.599899 · DOI
  31. Kabsch, 2010, XDS, Acta Crystallographica. Section D, Biological Crystallography, 66, 125, 10.1107/S0907444909047337 · DOI · Paper page
  32. Kidmose, 2019, Namdinator - automatic molecular dynamics flexible fitting of structural models into cryo-EM and crystallography experimental maps, IUCrJ, 6, 526, 10.1107/S2052252519007619 · DOI
  33. Kohler, 2018, Enterococcus adhesin PrgB facilitates type IV secretion by condensation of extracellular DNA, Molecular Microbiology, 109, 263, 10.1111/mmi.13994 · DOI
  34. Koraimann, 2018, Spread and Persistence of Virulence and Antibiotic Resistance Genes: A Ride on the F Plasmid Conjugation Module, EcoSal Plus, 8, 10.1128/ecosalplus.ESP-0003-2018 · DOI
  35. Larson, 2011, Crystal structure of the C-terminal region of Streptococcus mutans antigen I/II and characterization of salivary agglutinin adherence domains, The Journal of Biological Chemistry, 286, 21657, 10.1074/jbc.M111.231100 · DOI
  36. Lassinantti, 2021, Enterococcal PrgU Provides Additional Regulation of Pheromone-Inducible Conjugative Plasmids, mSphere, 6, 10.1128/mSphere.00264-21 · DOI
  37. Laverde Gomez, 2014, Is Essential for Conjugative Transfer of the Pheromone-Responsive Plasmid pCF10, Journal of Applied Microbiology, 196, 527, 10.1128/JB.00950-13 · DOI
  38. Maddocks, 2011, Streptococcus pyogenes antigen I/II-family polypeptide AspA shows differential ligand-binding properties and mediates biofilm formation, Molecular Microbiology, 81, 1034, 10.1111/j.1365-2958.2011.07749.x · DOI
  39. Mieher, 2018, Glucan Binding Protein C of Streptococcus mutans Mediates both Sucrose-Independent and Sucrose-Dependent Adherence, Infection and Immunity, 86, 1, 10.1128/IAI.00146-18 · DOI · Paper page
  40. Mieher, 2021, Structure-Function Characterization of Streptococcus intermedius Surface Antigen Pas, Journal of Bacteriology, 203, 10.1128/JB.00175-21 · DOI
  41. Muscholl, 1993, Sex pheromone plasmid pAD1-encoded aggregation substance of Enterococcus faecalis is positively regulated in trans by traE1, European Journal of Biochemistry, 214, 333, 10.1111/j.1432-1033.1993.tb17928.x · DOI
  42. Olmsted, 1991, Role of the pheromone-inducible surface protein Asc10 in mating aggregate formation and conjugal transfer of the Enterococcus faecalis plasmid pCF10, Journal of Bacteriology, 173, 7665, 10.1128/jb.173.23.7665-7672.1991 · DOI
  43. Olmsted, 1993, High-resolution visualization by field emission scanning electron microscopy of Enterococcus faecalis surface proteins encoded by the pheromone-inducible conjugative plasmid pCF10, Journal of Bacteriology, 175, 6229, 10.1128/jb.175.19.6229-6237.1993 · DOI
  44. Olmsted, 1994, A plasmid-encoded surface protein on Enterococcus faecalis augments its internalization by cultured intestinal epithelial cells, The Journal of Infectious Diseases, 170, 1549, 10.1093/infdis/170.6.1549 · DOI
  45. Palmer, 2010, Multidrug-resistant enterococci lack CRISPR-cas, mBio, 1, 10.1128/mBio.00227-10 · DOI
  46. Palmer, 2010, Horizontal gene transfer and the genomics of enterococcal antibiotic resistance, Current Opinion in Microbiology, 13, 632, 10.1016/j.mib.2010.08.004 · DOI
  47. Pettersen, 2004, UCSF Chimera--A visualization system for exploratory research and analysis, Journal of Computational Chemistry, 25, 1605, 10.1002/jcc.20084 · DOI
  48. Punjani, 2017, Building proteins in a day: Efficient 3D molecular structure estimation with electron cryomicroscopy, IEEE Transactions on Pattern Analysis and Machine Intelligence, 39, 706, 10.1109/TPAMI.2016.2627573 · DOI
  49. Purushotham, 2014, The calcium-induced conformation and glycosylation of scavenger-rich cysteine repeat (SRCR) domains of glycoprotein 340 influence the high affinity interaction with antigen I/II homologs, The Journal of Biological Chemistry, 289, 21877, 10.1074/jbc.M114.565507 · DOI
  50. Rakita, 1999, Enterococcus faecalis bearing aggregation substance is resistant to killing by human neutrophils despite phagocytosis and neutrophil activation, Infection and Immunity, 67, 6067, 10.1128/IAI.67.11.6067-6075.1999 · DOI
  51. Rego, 2016, Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae, The Journal of Biological Chemistry, 291, 15985, 10.1074/jbc.M116.726562 · DOI
  52. Schlievert, 2010, Enterococcus faecalis endocarditis severity in rabbits is reduced by IgG Fabs interfering with aggregation substance, PLOS ONE, 5, 10.1371/journal.pone.0013194 · DOI
  53. Schmitt, 2018, PrgB promotes aggregation, biofilm formation, and conjugation through DNA binding and compaction, Molecular Microbiology, 109, 291, 10.1111/mmi.13980 · DOI
  54. Schmitt, 2020, Enterococcal PrgA Extends Far Outside the Cell and Provides Surface Exclusion to Protect against Unwanted Conjugation, Journal of Molecular Biology, 432, 5681, 10.1016/j.jmb.2020.08.018 · DOI
  55. Süssmuth, 2000, Aggregation substance promotes adherence, phagocytosis, and intracellular survival of Enterococcus faecalis within human macrophages and suppresses respiratory burst, Infection and Immunity, 68, 4900, 10.1128/IAI.68.9.4900-4906.2000 · DOI
  56. Trokter, 2018, Correction for Trokter and Waksman, “Translocation through the Conjugative Type IV Secretion System Requires Unfolding of Its Protein Substrate.”, Journal of Bacteriology, 200, 10.1128/JB.00482-18 · DOI
  57. Vanek, 1999, Enterococcus faecalis aggregation substance promotes opsonin-independent binding to human neutrophils via a complement receptor type 3-mediated mechanism, FEMS Immunology and Medical Microbiology, 26, 49, 10.1111/j.1574-695X.1999.tb01371.x · DOI
  58. Waters, 2001, Analysis of Functional Domains of the Enterococcus faecalis Pheromone-Induced Surface Protein Aggregation Substance, Journal of Bacteriology, 183, 5659, 10.1128/JB.183.19.5659-5667.2001 · DOI
  59. Waters, 2003, The aggregation domain of aggregation substance, not the RGD motifs, is critical for efficient internalization by HT-29 enterocytes, Infection and Immunity, 71, 5682, 10.1128/IAI.71.10.5682-5689.2003 · DOI
  60. Waters, 2004, An amino-terminal domain of Enterococcus faecalis aggregation substance is required for aggregation, bacterial internalization by epithelial cells and binding to lipoteichoic acid, Molecular Microbiology, 52, 1159, 10.1111/j.1365-2958.2004.04045.x · DOI
  61. Willett, 2019, Exploiting biofilm phenotypes for functional characterization of hypothetical genes in Enterococcus faecalis, NPJ Biofilms and Microbiomes, 5, 10.1038/s41522-019-0099-0 · DOI
  62. Winn, 2001, Use of TLS parameters to model anisotropic displacements in macromolecular refinement, Acta Crystallographica. Section D, Biological Crystallography, 57, 122, 10.1107/s0907444900014736 · DOI

Metadata

Authors
Sun, W.-S., Lassinantti, L., Järvå, M., Schmitt, A., ter Beek, J., & Berntsson, R. P.-A.
Affiliations
Umeå University (SE)
Venue
eLife
Published
2023-10-20
Volume
12
ISSN
2050-084X (ISSN-L)
OpenAlex
W4387815499
Cited by
10
References
1
Citations by year
2025: 5 · 2024: 5
FWCI
0.89
Type
journal article
Language
en
Open access
Locations
eLife (publishedVersion, cc-by)
Funders
  • Vetenskapsrådet (2016-03599)
  • Kempestiftelserna (SMK-1762, SMK-1869)
  • Carl Tryggers Stiftelse för Vetenskaplig Forskning (CTS 18:39)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Microbiology › Escherichia coli research studies
Keywords
Enterococcus faecalis, conjugation, biofilm formation, bacterial virulence, type IV secretion system, immunoglobulin-like domains, protein structure, surface adhesins, mating pair formation, cell aggregation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review