The Non-Flagellar Type III Secretion System Evolved from the Bacterial Flagellum and Diversified into Host-Cell Adapted Systems
We propose that genes common to the flagellum and the NF-T3SS were present in the flagellar ancestor of NF-T3SS. They are designated as “T3SS genes”. Then we detail the evolution of this system to the extant NF-T3SSs. First, the loss of flagellum-specific genes resulted in loss of the motility function. Presumably this system kept the ability to translocate or secrete proteins. The ancestral NF-T3SS experienced a series of gene losses and gains while diversifying to the ancestor of all extant NF-T3SSs. One early lineage derived into the Myxo systems by loss of some genes, notably SctF. Acquisition of secretins and of a few other genes allowed the formation of ancestral contact-dependent protein secretion systems, and the concomitant ability to subvert eukaryotic cells by direct delivery of effectors in their cytosol. Secretins were recruited to the NF-T3SS at least three times from three different cell machineries. Finally, the NF-T3SS quickly diversified and adapted to different host cells. Some components of NF-T3SS, such as the translocon proteins (YopB/YopD), the needle length determinant (SctP) or the needle tip (LcrV), cannot yet be integrated in this schema because of low or undetectable sequence similarity among T3SSs. Structural and sequence similarities were previously noted between translocon proteins of Chlamydia (CopB) and Salmonella (SipB) . In contrast, we found no more than 28% identity over less than half of the protein when aligning CopB with all complete genomes in GenBank after excluding Chlamy proteins (Blastp, e-value>0.05). We also did not find significant sequence homologs of YopB/YopD in the NF-T3SS of Myxo or plant-associated bacteria. Since the translocon is required for protein delivery but not for secretion , it might have been acquired after the secretin. Balloons indicate gene losses and accretions. Only genes mentioned in the main text are shown. Abbreviated names of taxa are as in Figure 4.