Alpha hemolysin of Escherichia coli induces a necrotic-like procoagulant state in platelets.

Autor: Pérez Vázquez K; Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CCT- La Plata, CONICET. Facultad de Ciencias Médicas. Universidad Nacional de La Plata, Argentina., Tau J; Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CCT- La Plata, CONICET. Facultad de Ciencias Médicas. Universidad Nacional de La Plata, Argentina., Leal Denis MF; Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) 'Prof. Alejandro C. Paladini', Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina., Fader CM; Laboratorio de Biología Celular y Molecular, Instituto de Histología y Embriología, (IHEM), Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina; Facultad de Odontología, Universidad Nacional de Cuyo, Mendoza, Argentina., Ostuni MA; Université Paris Cité and Université des Antilles, INSERM, BIGR, F-75015, Paris, France., Schwarzbaum PJ; Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) 'Prof. Alejandro C. Paladini', Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina., Herlax V; Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CCT- La Plata, CONICET. Facultad de Ciencias Médicas. Universidad Nacional de La Plata, Argentina. Electronic address: vherlax@med.unlp.edu.ar.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2024 Dec; Vol. 227 (Pt A), pp. 1-14. Date of Electronic Publication: 2024 Jun 08.
DOI: 10.1016/j.biochi.2024.06.001
Abstrakt: Uropathogenic strains of E. coli (UPEC) is a leading cause of sepsis, deploying multiple virulence factors to evade host immune responses. Notably, alpha-hemolysin (HlyA) produced by UPEC is implicated in septic symptoms associated with bacteremia, correlating with thrombocytopenia, a critical indicator of organ dysfunction and a predictor of poorer patient prognosis. This study meticulously explores the impact of sublytic concentrations of HlyA on platelets. Findings reveal that HlyA triggers an increase in intracellular calcium, activating calpain and exposing phosphatidylserine to the cell surface, as validated by flow cytometric experiments. Electron microscopy reveals a distinctive balloon-like shape in HlyA-treated platelets, indicative of a procoagulant state. The toxin induces the release of procoagulant extracellular vesicles and the secretion of alpha and dense granules. Overall, the results point to HlyA inducing a necrotic-like procoagulant state in platelets. The effects of sublytic concentrations of HlyA on both erythrocytes and platelets could have a potential impact on capillary microcirculation. Targeting HlyA emerges as a viable therapeutic strategy to mitigate the adverse effects of UPEC infections, especially in South American countries where these infections are endemic, underscoring its significance as a potential therapeutic target.
Competing Interests: Declaration of competing interest The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
(Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
Databáze: MEDLINE
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