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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Foodborne Toxin Detection and Prevention Research » Research » Publications at this Location » Publication #407166
Research Project: Technologies for the Detection of Bacterial and Plant Toxins and Allergens that Impact Food Safety and Food Defense

Location: Foodborne Toxin Detection and Prevention Research

Title: Detection of cleaved Stx2a in the blood of STEC-infected patients

Author
item VARRONE, ELISA - University Of Bologna, Italy
item CARNICELLI, DOMENICA - University Of Bologna, Italy
item He, Xiaohua
item GRASSE, MARCO - Innsbruck Medical University
item STAMPFER, KARIN - Innsbruck Medical University
item HUBER, SILKE - Innsbruck Medical University
item KELLNEROVA, SARA - Innsbruck Medical University
item TAZZARI, PIER LUIGI - Hospital Policlinico S Orsola - Malpighi
item RICCI, FRANCESCA - Hospital Policlinico S Orsola - Malpighi
item PATERINI, PAOLA - University Of Bologna, Italy
item ARDISSINO, GIANLUIGI - Fondazione Irccs Ca’ Granda Ospedale Maggiore Policlinico
item MORABITO, STEFANO - Istituto Superiore Di Sanità
item ORTH-HOLLER, DOROTHEA - Innsbruck Medical University
item WURZNER, REINHARD - Innsbruck Medical University
item BRIGOTTI, MAURIZIO - University Of Bologna, Italy

Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/4/2023
Publication Date: 12/8/2023
Citation: Varrone, E., Carnicelli, D., He, X., Grasse, M., Stampfer, K., Huber, S., Kellnerova, S., Tazzari, P., Ricci, F., Paterini, P., Ardissino, G., Morabito, S., Orth-Holler, D., Wurzner, R., Brigotti, M. 2023. Detection of cleaved Stx2a in the blood of STEC-infected patients. Toxins. 15(12). Article 690. https://doi.org/10.3390/toxins15120690.
DOI: https://doi.org/10.3390/toxins15120690

Interpretive Summary: Shiga toxin 2 is the major virulence factor in Shiga toxin-producing E. coli (STEC) associated life-threatening hemolytic uremic syndrome (HUS). Recently, it was found that the functions of Stx2 change according to modifications of the toxin structure. In this study, the cleaved form of Stx2a was detected in STEC-infected patients for the first time. The cleaved Stx2a was found binding to neutrophils in 2 out of 3 HUS patients. This result suggests that the cleaved Stx2a may play an important role in the pathogenesis of HUS.

Technical Abstract: Typical hemolytic uremic syndrome (HUS) is mainly caused by STEC (Shiga toxins-producing Escherichia coli) releasing Shiga toxin 2 (Stx2). Different structures of this AB5 toxin have been de-scribed: uncleaved, with intact B and A chains; or cleaved, which have a single nick in the A chain resulting in two fragments, A1 and A2, connected by a disulfide bridge. Despite the same toxic effect on sensitive cells, the two forms are functionally different in their binding properties for circulating cells, serum components and complement factors, thus differently contributing to the pathogenesis of HUS. The outcome of STEC infections and the consequent onset of HUS could be influenced by the presence of uncleaved or cleaved forms of Stx2 circulating in patients’ blood. Cleaved Stx2 was identified and quantified for the first time in 4 out of 8 STEC-infected patients’ sera by a method based on the inhibition of cell-free translation, further validated by a cytotoxicity test (Vero cells) in the presence of a specific antibody against cleaved Stx2. Cleaved Stx2 was present in patients with toxins bound to neutrophils and in 2 out of 3 patients developing HUS. Although not mandatory for HUS development it could contribute to the severity of symptoms.