Abstract
Tc toxins were originally identified in entomopathogenic bacteria, which are important as biological pest control agents. Tc toxins are heteromeric exotoxins composed of three subunit types, TcA, TcB, and TcC. The C-terminal portion of the TcC protein encodes the actual toxic domain, which is translocated into host cells by an injectosome nanomachine comprising the other subunits. Currently the pathogenic roles and distribution of Tc toxins among different bacterial genera remain unclear. Here we have performed a comprehensive genome-wide analysis, and established a database that includes 1,608 identified Tc loci containing 2,528 TcC proteins in 1,421 Gram-negative and positive bacterial genomes. Our findings indicate that TcCs conform to the architecture of typical polymorphic toxins, with C-terminal hypervariable regions (HVR) encoding more than 100 different classes of putative toxic domains, most of which have not been previously recognized. Based on further analysis of Tc loci in the genomes of all Salmonella and Yersinia strains in EnteroBase, a “two-level” evolutionary dynamics scenario is proposed for TcC homologues. This scenario implies that the conserved TcC RHS core domain plays a critical role in the taxonomical specific distribution of TcC HVRs. This study provides an extensive resource for the future development of Tc toxins as valuable agrochemical tools. It furthermore implies that Tc proteins, which are encoded by a wide range of pathogens, represent an important versatile toxin superfamily with diverse pathogenic mechanisms.
Highlights
Selection pressures in complex environments have driven bacteria to evolve numerous strategies to transfer proteins into the cells of diverse eukaryotic and/or prokaryotic organisms [1]
Entomopathogenic bacteria deploy a range of toxins to combat their insect hosts
The Tc toxins were first identified in Photorhabdus as having potent oral toxicity to insects, with a mode of action distinct from the well-studied Bacillus thuringiensis Cry toxins
Summary
Selection pressures in complex environments have driven bacteria to evolve numerous strategies to transfer proteins into the cells of diverse eukaryotic and/or prokaryotic organisms [1]. Several specialized nanomachines have been described which are used to deliver specific effectors into target cells, including the well-studied type III and VI secretion systems and extracellular contractile injection systems [5,6,7,8]. These effector proteins have been shown to play key roles in the lifecycles of prokaryotes in a diversity of environments. The first described PTs, causing contact-dependent growth inhibition (CDI) was the CdiB/CdiA two-partner secretion (TPS) system It requires a small immunity protein (CdiI) to prevent self-intoxication and the sequences of the C-termini of CdiA proteins exhibit high variability [11,12]. PTs include a toxic protein, which has bipartite architecture, with a conserved N-terminal region fused to variable C-terminal toxic domain and a specific immunity protein which is required to confer self-protection against the toxin
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