2. Academic Validation
  3. An antibiotic derivative as a new potential tool in the prevention of hemolytic uremic syndrome

An antibiotic derivative as a new potential tool in the prevention of hemolytic uremic syndrome

  • iScience. 2025 Jul 7;28(8):113076. doi: 10.1016/j.isci.2025.113076.
Elisa Varrone 1,  Luciano Consagra 1,  Domenica Carnicelli 1,  Elisabetta Galassi 1,  Beatrice Munari 1,  Elisa Porcellini 1,  Marta Pluchino 1 2,  Giorgia Rossi 1,  Federico Parenti 1 3,  Catia Barboni 3,  Barbara Brunetti 3,  Francesca Ricci 4,  Pier Luigi Tazzari 4,  Francesco Manoli 5,  Ilse Manet 5,  Paola Paterini 1 6,  Gianluca Storci 4,  Massimiliano Bonafè 1,  Alejandro Hochkoeppler 7,  Anna Zaghini 3,  Stefano Morabito 8,  Gianluigi Ardissino 9,  Timo Vaara 10,  Martti Vaara 10,  Maurizio Brigotti 1
Affiliations

Affiliations

  • 1 Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126 Bologna, Italy.
  • 2 Reconstructive Orthopaedic Surgery and Innovative Techniques - Musculoskeletal Tissue Bank, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
  • 3 Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, Ozzano dell'Emilia, 40064 Bologna, Italy.
  • 4 IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
  • 5 Istituto per la Sintesi Organica e la Fotoreattività, Consiglio Nazionale delle Ricerche, 40129 Bologna, Italy.
  • 6 Center for Applied Biomedical Research-CRBA, University of Bologna, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
  • 7 Department of Pharmacy and Biotechnology, University of Bologna, 40136 Bologna, Italy.
  • 8 European Reference Laboratory for Escherichia coli, Istituto Superiore di Sanità, 00161 Rome, Italy.
  • 9 Center for HUS Control, Prevention and Management, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
  • 10 Northern Antibiotics Ltd, 00140 Helsinki, Finland.
PMID: 40740497 DOI: 10.1016/j.isci.2025.113076
Abstract

Hemolytic uremic syndrome (HUS), the main cause of acute renal failure in early childhood, is associated with infections by Escherichia coli strains producing Shiga toxin 2 (Stx2). The microangiopathic injuries caused by the toxin occur mainly in the renal microvasculature when the glycolipid receptor globotriaosylceramide (Gb3Cer) is targeted. Before entering the kidney, Stx2 binds to circulating cells through Gb3Cer and Toll-like Receptor 4 (TLR4) and is subsequently delivered in extracellular vesicles to target cells. Here, we have found a specific inhibitor of the Stx2/TLR4 interaction, the preclinical polymyxin B derivative NAB815. The compound impairs the formation of Stx2-containing extracellular vesicles produced by leukocytes and platelets and also reduces their toxic effects in cellular (Vero cells) and animal models (CD-1 mice). NAB815 would represent a useful tool in preventing HUS and is effective at sub-bactericidal concentrations, thus overcoming the concern that Antibiotics are harmful to patients infected with Stx2-producing E. coli.

Keywords

Biological sciences; Medical Microbiology; Microbiology; Natural sciences; Pharmacology.

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