Abstract
Mono-ADP-ribosyl transferase (mART) proteins are secreted virulence factors produced by several human pathogens, the founding member being diphtheria toxin (DT). Pseudomonas aeruginosa can also secrete a mART toxin, known as exotoxin A (PE), but with an organization of its three functional domains (receptor, translocation, and enzymatic elements) that is opposite to DT. Two additional PE-like toxins (PLTs) have been identified from Vibrio cholerae and Aeromonas hydrophila, suggesting more PLT family members may exist. Database mining discovered six additional putative homologues, considerably extending this group of PLTs across a wide range of bacterial species. Here, we examine sequence and structural information for these new family members with respect to previously identified PLTs. The X-ray crystal structures of four new homologues show the conservation of critical features responsible for structure and function. This study shows the potential of these newly described toxins for the development of novel drug delivery platforms. Additionally, genomic analysis suggests horizontal gene transfer to account for the wide distribution of PLTs across a range of eubacteria species, highlighting the need to monitor emerging pathogens and their virulence factors.
| Original language | English |
|---|---|
| Article number | 413 |
| Journal | Communications Biology |
| Early online date | 11 Mar 2025 |
| DOIs | |
| Publication status | E-pub ahead of print - 11 Mar 2025 |
Data Availability Statement
The atomic coordinates and structure factors (PDB codes 9G7M, 9G7N, 9G7O, and 9G7P) have been deposited in the Protein Data Bank (http:// wwpdb.org).Datasetsgeneratedduringthecurrentstudyareavailablefrom the corresponding author upon reasonable request. Original data for Fig. 3f, g are provided in Supplementary Data 1, and pictures for Fig. 4 are available in Supplementary Fig. 5.Acknowledgements
We thank the scientists at stations I03 and I04 of the Diamond Light Source, Didcot, Oxfordshire (UK) for their support during X-ray data collection (proposals mx-23269 and mx-21265). G.M. was supported by a Research Fellowship from Applied Molecular Transport Inc. (San Francisco, CA, USA) at the University of Bath (UK). This work was supported by research grants from Applied Molecular Transport Inc.Funding
University of Bath - G.M. was supported by a Research Fellowship from Applied Molecular Transport Inc. (San Francisco, CA, USA) at the University of Bath (UK). This work was supported by research grants from Applied Molecular Transport Inc.