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Updated: Sep 18, 2025

Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins
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Phage Phenomics: Physiological Approaches to Characterize Novel Viral Proteins

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Structure of the virulence-associated Neisseria meningitidis filamentous bacteriophage MDAΦ

Jan Böhning1, Miles Graham1, Mathieu Coureuil2

  • 1Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom.

Proceedings of the National Academy of Sciences of the United States of America
|June 20, 2025
PubMed

Insights

Researchers revealed the structure of the MDA bacteriophage (MDAΦ) from the pathogen Neisseria meningitidis. This filamentous phage promotes bacterial invasion and infection by facilitating adhesion and biofilm formation.

Area of Science:

  • Microbiology
  • Structural Biology
  • Virology

Background:

  • Neisseria meningitidis is a human pathogen causing life-threatening meningitis and septicemia.
  • Hyperinvasive strains often express the MDA bacteriophage (MDAΦ), crucial for mucosal colonization and invasion.
  • The molecular mechanisms of MDAΦ's role in biofilm formation and infection remain unclear.

Purpose of the Study:

  • To determine the structure and organization of the MDA bacteriophage (MDAΦ).
  • To elucidate the molecular mechanisms underlying MDAΦ's role in Neisseria meningitidis pathogenesis.
  • To provide insights into the evolution and diversity of filamentous bacteriophages.

Main Methods:

  • Electron cryomicroscopy (cryo-EM) was used to determine the structure of the MDA phage.
  • Electron cryotomography (cryo-ET) was employed to analyze phage bundles and higher-order assembly.
  • Comparative analysis with other filamentous bacteriophages was performed.

Main Results:

  • The MDAΦ was characterized as a class I filamentous inovirus with a highly curved, densely packed major capsid protein (MCP) structure.
  • A disordered N-terminal segment of the MCP exposes hydrophobic patches, mediating phage-phage interactions.
  • These interactions provide a structural basis for previously observed epithelial adhesion and infection.

Conclusions:

  • The study reveals the detailed structure and assembly of the MDA phage, a key virulence factor in Neisseria meningitidis.
  • Insights into phage-phage interactions offer a molecular explanation for enhanced bacterial adhesion and pathogenicity.
  • This work contributes to understanding phage evolution, bacterial adhesion mechanisms, and the pathogenicity of N. meningitidis.
Keywords:
Neisseriabiofilmcryo-EMcryo-ETinoviral phage

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