# Neisseria meningitidis filamentous phage MDA promotes colonisation by selecting hyperadhesive pili variants

**Authors:** Clémence Mouville, Antoine Brizard, Morgane Wuckelt, Mélanie Montabord, Hervé Lécuyer, Julie Meyer, Anne Jamet, Béatrice Durel, Charlotte Izabelle, Xavier Nassif, Mathieu Coureuil, Emmanuelle Bille

PMC · DOI: 10.1038/s41467-025-67441-w · Nature Communications · 2025-12-20

## TL;DR

A filamentous phage in Neisseria meningitidis promotes bacterial colonization by targeting and selecting hyperadhesive bacteria.

## Contribution

The study reveals that the MDA phage preferentially infects and amplifies meningococci with hyperadhesive pili through antigenic variation.

## Key findings

- MDA phage binds along the entire length of type IV pili, favoring positively charged pilin variants.
- Bacteria with more positively charged pilin are more adhesive and targeted by MDA phage.
- Adhesion to human cells amplifies the population of phage-infected meningococci.

## Abstract

Filamentous phages are non-lytic phages mutually beneficial to their bacterial hosts. In Neisseria meningitidis, the filamentous phage MDA is associated with invasive diseases thanks to its key role in the formation of biofilm during epithelium colonisation. The infection model for filamentous phages has been defined for phages Ff and CTX. These phages bind to the tips of bacterial pili before being translocated into the periplasm of their hosts. The aim of this study is to investigate the relationship between filamentous phage infection and type IV pili, using the bacterium Neisseria meningitidis and the bacteriophage MDA as model organisms. We show that MDAΦ rather binds to type IV pili along their entire length with preferential binding to positively charged variants of the major fibre-forming pilin, demonstrating a role for antigenic variation in phage infection. Strikingly, bacteria expressing the more positively charged pilin are also the most adhesive, suggesting that MDAΦ primarily target the most adhesive bacteria. Finally, we show that adhesion to human cells is sufficient to amplify the phage-positive meningococcal population. Overall, this study reveals how a filamentous phage can target hyperadhesive bacterial variants and promote their selection, thereby establishing a link between phage infection and bacterial colonisation.

In Neisseria meningitidis, the filamentous phage MDA is associated with biofilm formation during epithelium colonisation. Here, the authors investigate the relationship between phage MDA infection and type IV pili in N. meningitidis.

## Linked entities

- **Proteins:** pilin (fimbrial subunit)
- **Species:** Neisseria meningitidis (taxon 487)

## Full-text entities

- **Diseases:** infection (MESH:D007239), invasive (MESH:D009361), Neisseria meningitidis (MESH:D006069)
- **Chemicals:** MDAPhi (-), MDA (MESH:D015104)
- **Species:** Neisseria meningitidis (species) [taxon 487], Bacteriophage sp. (species) [taxon 38018], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12819557/full.md

## References

5 references — full list in the complete paper: https://tomesphere.com/paper/PMC12819557/full.md

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Source: https://tomesphere.com/paper/PMC12819557