This page has only limited features, please log in for full access.
AB5 protein toxins are produced by certain bacterial pathogens and are composed of an enzymatically active A-subunit and a B-subunit pentamer, the latter being responsible for cell receptor recognition, cellular uptake, and transport of the A-subunit into the cytosol of eukaryotic target cells. Two members of the AB5 toxin family were described in Shiga toxin-producing Escherichia coli (STEC), namely Shiga toxin (Stx) and subtilase cytotoxin (SubAB). The functional paradigm of AB toxins includes the B-subunit being mandatory for the uptake of the toxin into its target cells. Recent studies have shown that this paradigm cannot be maintained for SubAB, since SubA alone was demonstrated to intoxicate human epithelial cells in vitro. In the current study, we raised the hypothesis that this may also be true for the A-subunit of the most clinically relevant Stx-variant, Stx2a. After separate expression and purification, the recombinant Stx2a subunits StxA2a-His and StxB2a-His were applied either alone or in combination in a 1:5 molar ratio to Vero B4, HeLa, and HCT-116 cells. For all cell lines, a cytotoxic effect of StxA2a-His alone was detected. Competition experiments with Stx and SubAB subunits in combination revealed that the intoxication of StxA2a-His was reduced by addition of SubB1-His. This study showed that the enzymatic subunit StxA2a alone was active on different cells and might therefore play a yet unknown role in STEC disease development.
Laura Heinisch; Maike Krause; Astrid Roth; Holger Barth; Herbert Schmidt. Cytotoxic Effects of Recombinant StxA2-His in the Absence of Its Corresponding B-Subunit. Toxins 2021, 13, 307 .
AMA StyleLaura Heinisch, Maike Krause, Astrid Roth, Holger Barth, Herbert Schmidt. Cytotoxic Effects of Recombinant StxA2-His in the Absence of Its Corresponding B-Subunit. Toxins. 2021; 13 (5):307.
Chicago/Turabian StyleLaura Heinisch; Maike Krause; Astrid Roth; Holger Barth; Herbert Schmidt. 2021. "Cytotoxic Effects of Recombinant StxA2-His in the Absence of Its Corresponding B-Subunit." Toxins 13, no. 5: 307.
The ability to produce enterohemolysin is regarded as a potential virulence factor for enterohemorrhagic Escherichia coli (EHEC) and is frequently associated with severe human diseases such as hemorrhagic colitis (HC) and the hemolytic uremic syndrome (HUS). The responsible toxin, which has also been termed EHEC-hemolysin (EHEC-Hly, syn. Ehx), belongs to the Repeats in Toxin (RTX)-family of pore-forming cytolysins and is characterized by the formation of incomplete turbid lysis zones on blood agar plates containing defibrinated sheep erythrocytes. Besides the expression of Shiga toxins (Stx) and the locus of enterocyte effacement (LEE), EHEC-Hly is a commonly used marker for the detection of potential pathogenic E. coli strains, although its exact role in pathogenesis is not completely understood. Based on the current knowledge of EHEC-Hly, this review describes the influence of various regulator proteins, explains the different mechanisms leading to damage of target cells, discusses the diagnostic role, and gives an insight of the prevalence and genetic evolution of the toxin.
Maike Schwidder; Laura Heinisch; Herbert Schmidt. Genetics, Toxicity, and Distribution of Enterohemorrhagic Escherichia coli Hemolysin. Toxins 2019, 11, 502 .
AMA StyleMaike Schwidder, Laura Heinisch, Herbert Schmidt. Genetics, Toxicity, and Distribution of Enterohemorrhagic Escherichia coli Hemolysin. Toxins. 2019; 11 (9):502.
Chicago/Turabian StyleMaike Schwidder; Laura Heinisch; Herbert Schmidt. 2019. "Genetics, Toxicity, and Distribution of Enterohemorrhagic Escherichia coli Hemolysin." Toxins 11, no. 9: 502.