A novel immunity system for bacterial nucleic acid degrading toxins and its recruitment in various eukaryotic and DNA viral systems

Zhang, Dapeng; Iyer, Lakshminarayan M.; Aravind, L.

In Actinobacteria, but not firmicutes, we observed several large proteins with architectures similar to the CDIs of the proteobacteria. These typically contain RHS repeats; however, their extreme N-terminal domains did not bear any close relationship to the proteobacterial TpsA-SD. Instead they were found to contain an N-terminal signal peptide and some of these proteins (e.g. gi: 256812841, a protein from S. griseus) contain multiple lamininG domains embedded within repetitive regions. The protein DIP1652 (gi: 38234225) from C. diphtheria shows another distinct low complexity repeat N-terminal to the nuclease domain ( Figure 5 ) and like in the above case it also possesses a conventional signal peptide. Likewise, a distinctive signal peptide, which is highly conserved in multiple proteins only within the genus Planctomyces, is seen in predicted nuclease toxins from this organism (e.g. gi: 149178028). Another group of large toxin proteins with RHS repeats, which predominantly occur in proteobacteria, are defined by the presence of repeats of the PAAR domain (PFAM: PF05488) N-terminal to the RHS repeats. All these proteins are typified by the presence of a conserved transmembrane domain with two TM segments ( Figure 5 and Supplementary Data) just N-terminal to the PAAR domains. We propose that these TM segments are required for their trafficking to the cell membrane, following which they might be processed in the periplasm for release via the outer membrane in a process that might depend on the PAAR domains. We also noticed a comparable domain with two TM segments in few firmicutes (e.g. gi: 125974537 from C. thermocellum) and in chlamydiae (e.g. 189219187 from M. infernorum, which is a rare case of the nuclease domain occurring N-terminal to the two TM domain; Figure 5 ). These proteins lack PAAR domains but the firmicute versions have additional hedgehog-intein (HINT) peptidase domains (see below) that could aid in their release on the cell-surface ( Figure 5 ). These observations suggest that at least some nuclease toxins in bacterial lineages such as actinobacteria, bacteroidetes and planctomycetes with conventional signal peptides, and those in proteobacteria, chlamydiae and firmicutes with two-TM domains are probably delivered to the cell using the conventional Sec-dependent system (68) . In the context of the above cases, it is of interest to note that E. coli Syd, an archetypal member of the SUKH superfamily, was first identified as a possible proof-reading component of the Sec-dependent export system (43) (44) (45) . In this context it is possible that the binding of certain members of the SUKH superfamily (at least the Syd-like group) in the producing cell might not only help in conferring immunity to 'self' but also in guiding the 'pro-toxin' to the Sec-dependent export machinery.