Association of α-hemolysin-induced morphological changes with platelet functional alterations

KENIA PÉREZ VÁZQUEZ; MARIA FLORENCIA LEAL DENIS; PABLO SCHWARZBAUM; VANESA HERLAX

Congreso; LI Reunión Anual de la Sociedad Argentina de Biofísica; 2023

Urinary tract infections, primarily attributed to uropathogenic Escherichia coli (UPEC),initiate with bladder colonization and, if left untreated, progress through the ureters to thekidneys, where bacteria can gain access to the bloodstream (bacteremia). UPEC hasdeveloped various virulence factors, with α-hemolysin (HlyA) being particularly notabledue to its cytolytic capability on host cells with α-hemolysin (HlyA) being particularlynotable due to its cytolytic capability on host cells, facilitating the dissemination ofinfection and remaining one of the most predominant factors in antibiotic-resistant UPECstrains. Platelets, crucial for maintaining homeostasis, also respond dynamically to thepresence of pathogens, enhancing their procoagulant activity and potentially leading tocell death. In this study, we examined the morphology and function of human plateletswhen exposed to HlyA in an in vitro bacteremia model. Electron microscopy revealedsignificant changes in platelet surface and ultrastructure, exhibiting features of anecrotic-like procoagulant phenotype, such as the release of granules and thetransformation into balloon-shaped platelets, associated with impaired functions likeextracellular ATP production, aggregation, spreading, and clot retraction measured byluminometry, light transmission, flow cytometry, and confocal microscopy. Our findingsprovide insights into the interaction between human platelets and HlyA, and thus themechanisms that could affect homeostasis and coagulation during UPEC infections.