About the Toxin complex (Tc)

The Tc toxins are first characterized in Photorhabdus luminescens (Bowen et al., 1998). Examples of the Tc toxin have been shown to exhibit potent oral toxicity towards certain insects. This led to its initial description primarily as an insecticidal toxin (Bowen and Ensign, 1998; Waterfield et al., 2005). Indeed, the Tc locus has been found in several types of entomopathogenic bacteria, including Xenorhabdus nematophila (Sergeant et al., 2003), Serratia entomophila (Hurst et al., 2000) and Yersinia entomophaga (Hurst et al., 2011).

Several Tc toxins have been shown to comprise three subunit components collectively referred to as TcA, TcB and TcC. Together they form an injection device in a 5:1:1 stoichiometry (Roderer et al., 2019). Five molecules of TcA form a bell-shaped pentamer with a central channel surrounded by a shell (Gatsogiannis et al., 2013). The TcB and TcC subunits form a heterodimer displaying a cocoon-like structure, the shell of which mainly consists of β-strands derived from both proteins (Busby et al., 2013). The C terminal hyper-variable region (HVR) of TcC is the toxin "bullet" of the system and is located within the lumen of this cocoon. As the enzymatically active part of the Tc toxin, the C terminal HVR can be delivered into target cells through a channel formed by conformational changes within the TcA pentamer (Gatsogiannis et al., 2018).

About the database

Based on selected characteristics of functionally confirmed Tc toxins, we developed a protein HMM profile and genomic context-based approach for the large-scale identification of potential Tc loci in publicly available bacterial genomes. With this approach, a phylogenetically diverse and broadly distributed superfamily of putative Tc loci was identified from 279 complete and 1,142 draft bacterial genomes available from GenBank, as of March 2019. The 1,608 Tc loci cover both Gram-negative and Gram-positive bacteria. Therefore, dbTC, a dedicated database summarizing current information of these putative Tc loci was constructed to facilitate future studies.

The database was produced from a collaborative project of

• National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College
  • Lihong Chen, Bo Liu, Jian Yang
• Beijing Friendship Hospital, Capital Medical University
  • Nan Song, Guowei Yang
• Warwick Medical School, Warwick University
  • Zhemin Zhou, Nicholas R. Waterfield

Publication

Nan Song, Lihong Chen, Zhemin Zhou, Xingmei Ren, Bo Liu, Siyu Zhou, Caihong Wang, Yun Wu, Nicholas R. Waterfield, Jian Yang, Guowei Yang, 2021. Genome-wide dissection reveals diverse pathogenic roles of bacterial Tc toxins. PLOS Pathogens. 17(2):e1009102.

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