Export of Vibrio cholerae RTX toxin

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><p><em>Vibrio cholerae</em>, the causative agent of the severe diarrheal disease cholera, secretes several "accessory" toxins including RTX toxin, which causes cross-linking of the actin cytoskeleton. The rtx locus of <em>V. cholerae</em> is located adjacent to the integrated CTX? prophage. The RTX toxin itself is encoded by the <em>rtxA</em> gene found in an operon with conserved hypothetical gene VC1449 and <em>rtxC</em>. The divergently transcribed <em>rtx</em> operon encodes three components of an atypical type I secretion system (T1SS) that includes a total of four secretion proteins. The T1SS components encoded by <em>rtxB, rtxD, rtxE</em>, and <em>tolC</em> are essential for secretion of the RTX toxin to supernatant fluids. When secretion is blocked, these TISS mutants accumulate active toxin intracellulary. Mutation of the nucleotide-binding sites of either RtxB or RtxE blocked secretion of the RTX toxin, thus showing that, unlike other RTX toxin secretion apparatus, the T1SS of <em>V. cholerae</em> requires two distinct ATPases. Since the discovery of the RTX toxin, seven related toxins in four different species have been identified, and an analysis of the genomic structure upstream of the <em>rtxA</em>-like toxin genes revealed that all share synteny and encode an atypical T1SS, suggesting that this is a common feature of toxins similar to the <em>V. cholerae</em> RTX toxin.</p> <p>It was previously noted that RTX-associated activity is only detectable in supernatant fluids from log phase cultures. Subsequently, the means for regulating RTX toxin activity in supernatant fluids were investigated. Exported proteases are capable of destroying RTX activity and may therefore play a role in the growth phase regulation of toxin activity. It was determined that the absence of RTX toxin in stationary phase culture supernatant fluids is also due to a lack of toxin secretion and not solely attributable to proteolytic inactivation. The T1SS apparatus is regulated at the transcriptional level by growth phase control that is independent of quorum sensing, unlike other virulence factors of <em>V. cholerae</em>. Additionally, the RTX toxin itself is regulated at the transcriptional level by growth phase, and in stationary phase cultures, all RTX toxin activity is associated with bacterial membranes or outer membrane vesicles.</p>

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  • 05/14/2018
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