Fig. 1: In-vivo vlhA switching and disease progression in the absence (A) and in the presence (B) of preformed antibodies against MG.

A The current working model of ordered VlhA switching of MG in response to the changing respiratory epithelial phenotype during infection. Loose attachment to ciliary cells with VlhA proteins transitions to tight attachment on the cell membrane with both VlhA proteins and the cytadhesins GapA and CrmA, utilizing gliding motility mechanisms. As epithelial phenotypes change, so do their surface molecules, and vlhA gene expression in the bacterium changes to allow for continued adhesion to host cells. B In the presence of a vaccine that contains all the VlhA antigens that are expressed early in MG infection, phase variation is not allowed to progress. Even the rare bacterial cell that manages to evade antibodies and attach to host cells will be targeted when VlhA switching occurs, as antibodies are present against these subsequent VlhA proteins as well. The addition of GapA and CrmA antigens further helps to ensure that attachment of MG bacteria to host respiratory epithelium is minimized.