Serogroup-specific Interaction of Neisseria meningitidis Capsular Polysaccharide with Host Cell Microtubules and Effects on Tubulin Polymerization

We have previously shown that during the late stages of the infectious process serogroup B meningococci (MenB) are able to escape the phagosome of in vitro-infected human epithelial cells. Then, they multiply in the cytosolic environment and spread intracellularly and to surrounding cells by exploiting the microtubule cytoskeleton as suggested by results of infections in the presence of microtubule inhibitors and the evidence of "nanotubes" connecting neighboring cells. In this study, by using microtubule binding assays with purified microtubule "asters" and "bundles" and microtubule "bundles" synthesized in vitro we demonstrate that the MenB capsule directly mediates the interaction between bacteria and microtubules. The direct interaction between the microtubules and the MenB capsular polysaccharide was confirmed by co-immunoprecipitation experiments. Unexpectedly, serogroup C meningococci (MenC), which have a capsular polysaccharide that differs from that of MenB only by its anomeric linkage, α(2→9) instead of α(2→8), were not able to interact with the microtubules, and the lack of interaction was not due to capsular polysaccharide O-acetylation that takes place in most of MenC strains but not in MenB. Moreover, we demonstrate that the MenB capsular polysaccharide inhibits tubulin polymerization in vitro. Thus, at variance with MenC, MenB may interfere with microtubule dynamics during cell infection.