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Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
Neisseria meningitidis filamentous phage MDA promotes colonisation by selecting hyperadhesive pili variants
Clémence Mouville1, Antoine Brizard1, Morgane Wuckelt1
1Institut Necker-Enfants Malades, INSERM U1151, CNRS UMR8253, Université Paris Cité, Paris, France.
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.
Insights
Filamentous phage MDA targets hyperadhesive Neisseria meningitidis by binding to type IV pili. This interaction promotes the selection of more adhesive bacteria, linking phage infection to enhanced bacterial colonization.
Area of Science:
- Microbiology
- Virology
- Bacterial Pathogenesis
Background:
- Filamentous phages are non-lytic viruses that can benefit their bacterial hosts.
- In Neisseria meningitidis, the MDA phage is linked to invasive diseases via biofilm formation during epithelial colonization.
- Existing models show filamentous phages binding to bacterial pili tips for entry.
Purpose of the Study:
- To investigate the interaction between filamentous phage MDA and type IV pili in Neisseria meningitidis.
- To understand how phage infection influences bacterial adhesion and colonization.
Main Methods:
- Utilized Neisseria meningitidis and bacteriophage MDA as model organisms.
- Analyzed phage binding patterns to type IV pili variants.
- Assessed the correlation between pilin charge, bacterial adhesion, and phage infection.
- Studied the amplification of phage-positive populations upon adhesion to human cells.
Main Results:
- MDA phage binds along the entire length of type IV pili, with a preference for positively charged pilin variants.
- Bacteria expressing more positively charged pilin exhibit higher adhesion to human cells.
- MDA phage preferentially targets and amplifies the most adhesive bacterial variants.
- Adhesion to human cells is sufficient to increase the population of phage-infected meningococci.
Conclusions:
- Filamentous phage MDA employs antigenic variation in type IV pili for host targeting.
- The phage selects for hyperadhesive bacterial strains, linking phage infection to enhanced colonization.
- This mechanism highlights a strategy where phages promote the success of their bacterial hosts in colonizing human cells.
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