Type II secretion and type IV pili of Francisella.

Francisella tularensis genomes encode homologues of type IV pili. Though several F. tularensis genes required for Tfp expression are homologous to genes required for type II secretion (T2S), these gene clusters mainly bear structural signatures that are typical of Tfp. There is preliminary evidence that different F. tularensis subspecies express Tfp-like surface structures, but there are also some interesting differences between the subspecies. One difference between the nonpathogenic subspecies novicida (F. novicida) and the highly pathogenic type A strains is in sequence of one of the predicted pilin genes, pilA. In contrast, type B strains show several differences compared to type A strains, two predicted pilin genes and the pilT gene are pseudogenes, while pilA is identical to pilA that is encoded by the type A strains. This is likely significant as PilA contributes to virulence of type B strains while PilT is essential for Tfp retraction in other bacterial pathogens. Tfp-mediated protein secretion is only evident in in vitro grown F. novicida. Surprisingly, secretion of several F. novicida proteins was dependent on pilA and other genes with postulated roles in Tfp expression. F. novicida secretion mutants were more virulent in the mouse infection model. Thus, in F. novicida, Tfp gene clusters serve both T2S and Tfp assembly and it is tempting to speculate that evolution of the pathogenic subspecies involved loss of functional T2S via structural changes of PilA and additional genes, including those that encode some of the Tfp-secreted proteins.