Several New Putative Bacterial ADP-Ribosyltransferase Toxins Are Revealed from In Silico Data Mining, Including the Novel Toxin Vorin, Encoded by the Fire Blight Pathogen Erwinia amylovora
| Autor: | Jennifer Geddes-McAlister, Allan (Rod) Merrill, Zachary Thow, Olivier Tremblay |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Health
Toxicology and Mutagenesis In silico lcsh:Medicine Bacterial genome size Erwinia Toxicology medicine.disease_cause Article 03 medical and health sciences Erwinia amylovora medicine Pathogen bacterial toxins 030304 developmental biology Genetics 0303 health sciences agriculture diseases integumentary system biology 030306 microbiology Effector lcsh:R Pathogenic bacteria biology.organism_classification toxin-antitoxin Yeast 3. Good health mono-ADP-ribosyltransferase toxins Fire blight |
| Zdroj: | Toxins Volume 12 Issue 12 Toxins, Vol 12, Iss 792, p 792 (2020) |
| ISSN: | 2072-6651 |
| DOI: | 10.3390/toxins12120792 |
| Popis: | Mono-ADP-ribosyltransferase (mART) toxins are secreted by several pathogenic bacteria that disrupt vital host cell processes in deadly diseases like cholera and whooping cough. In the last two decades, the discovery of mART toxins has helped uncover the mechanisms of disease employed by pathogens impacting agriculture, aquaculture, and human health. Due to the current abundance of mARTs in bacterial genomes, and an unprecedented availability of genomic sequence data, mART toxins are amenable to discovery using an in silico strategy involving a series of sequence pattern filters and structural predictions. In this work, a bioinformatics approach was used to discover six bacterial mART sequences, one of which was a functional mART toxin encoded by the plant pathogen, Erwinia amylovora, called Vorin. Using a yeast growth-deficiency assay, we show that wild-type Vorin inhibited yeast cell growth, while catalytic variants reversed the growth-defective phenotype. Quantitative mass spectrometry analysis revealed that Vorin may cause eukaryotic host cell death by suppressing the initiation of autophagic processes. The genomic neighbourhood of Vorin indicated that it is a Type-VI-secreted effector, and co-expression experiments showed that Vorin is neutralized by binding of a cognate immunity protein, VorinI. We demonstrate that Vorin may also act as an antibacterial effector, since bacterial expression of Vorin was not achieved in the absence of VorinI. Vorin is the newest member of the mART family further characterization of the Vorin/VorinI complex may help refine inhibitor design for mART toxins from other deadly pathogens. |
| Databáze: | OpenAIRE |
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