Vorin and Garvin are novel bacterial mono-ADP-ribosyltransferase toxins
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Abstract
Mono-ADP-ribosyltransferase (mART) toxins are secreted by several pathogenic bacteria that disrupt vital host cell processes in malignant diseases like cholera and whooping cough. Due to the 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. Using this bioinformatics approach, two mART toxins, Vorin and Garvin, encoded by the pathogens, Erwinia amylovora and Lactococcus garvieae, respectively, were discovered. Their cytotoxic effect was demonstrated in a eukaryotic cell growth assay. Catalytic variants failed to cause a growth-deficient phenotype, confirming the observed toxicity was enzymatic. Purification of Vorin required co-expression with a cognate binding partner, while Garvin was successfully purified to homogeneity. Preliminary functional and structural characterization was performed on both toxins. The study of Vorin and Garvin could yield treatment options against the diseases fire blight and lactococcosis by uncovering the toxin mechanisms responsible for their progression.