A filamentous phage promotes meningococcal colonization by selecting hyperadhesive pili variants linking phage infection to bacterial virulence

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Abstract
Filamentous phages belong to Inoviruses, a family of non-lytic phages that are mutually beneficial to their bacterial hosts. These phages have a role in bacterial dissemination, biofilm formation or immune evasion. In Neisseria meningitidis, the strains harbouring the MDA filamentous phage are associated with invasive diseases through the MDAΦ key role in epithelial cell colonisation. Using MDAΦ and N. meningitidis as model organisms, we aimed to understand the relationship between filamentous phage infection, type IV pili antigenic variation and bacterial colonisation. The paradigm of filamentous phage infection has been defined for the phages Ff and CTX, where binding to the tips of bacterial type IV pili is a means of infecting their bacterial host. In contrast, we showed that MDAΦ binds N. meningitidis type IV pili along the length of the filament, rather than at the tip, with preferential binding to positively charged variants of PilE (the major fibre-forming pilin) demonstrating a role for antigenic variation in phage infection. Strikingly, bacteria expressing the more positively charged PilE were the most adhesive, meaning that MDAΦ primarily target the most adhesive bacteria. Finally, we showed that adhesion to human cells is sufficient to amplify the phage-positive meningococcal population. Taken together, this study reveals how the propagation strategy of a filamentous phage, aimed at selecting the best coloniser as a host, can promote the selection of hyperadhesive bacterial variants, linking phage infection to bacterial virulence.

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