Interactions with Host Cells Causes Neisseria meningitidis Pili to Become Unglued

can be posttranslationally modified by phosphoethanolamine (PE), phosphocholine (PC), phosphoglycerol (PG), and by O-linked glycosylation. Several serine residues within the N. meningitidis pilin, as well as pilin from the closely related N. gonorrhoeae, have been shown to undergo modification. Serine 63 is modified by O-linked glycosylation, serine 68 is modified by either PE or PC, and PG has been identified as a modification of serine 93 (Stimson et al., 1995, 1996; Forest et al., 1999; Hegge et al., 2004). These post-translational modifications in turn exert an influence on pilus morphology and pilus-mediated adherence to human cells, as loss of glycosylation increases N. meningitidis adherence (Marceau et al., 1998), and loss of the PE/ PC modification results in increased pilus bundling in N. gonorrhoeae, but does not affect adherence (Forest et al., 1999). The genes involved in mediating glycosylation and PE/PC addition have been identified (Warren and Jennings, 2003; Hegge et al., 2004), but the enzyme responsible for PG addition was unknown. Chamot-Rooke et al. (2011) identified a N. meningitidis gene which is upregulated several-fold upon host cell contact, and which is responsible for adding phosphoglycerol (PG) to pilin subunits at serine residue 93. Mutation of the pilin phosphotransferase B (pptB) gene (NMV_0885), an ortholog of other phosphoglycerol transferases, resulted in a total loss of PG modification, and induction of a pptB gene under lac promoter control resulted in increased PG modification. Molecular modeling of the region surrounding serine 93 suggests that it carries a highly positive charge, which would be disturbed by the addition of a negatively charged PG group, which in turn was predicted to destabilize interactions between adjacent pilus fibers within a bundle. Consistent with this hypothesis, the induction of PptB expression and PG modification resulted in a decrease in pilus bundling, and a transition to expression Interactions with host cells causes Neisseria meningitidis pili to become unglued