Deleterious consequences of Shiga toxin in the CNS

SUMMARYThe primary objective of this review is to provide an update on the most recent findings concerning the adverse effects of Shiga toxin-producing <i>Escherichia coli</i> (STEC) on the central nervous system (CNS), from both clinical and experimental perspectives. Considered the main predictor of death, STEC encephalopathy plays a critical role in hemolytic uremic syndrome (HUS), which affects between 11% and 64% of HUS patients and considerably increases the risk of morbidity and mortality. Of note, STEC encephalopathy in the absence of HUS has been observed in approximately 5% of cases. The ability of enterohemorrhagic <i>E. coli</i> to adapt to its microenvironment has been responsible for global outbreaks. Once in circulation, Shiga toxin rapidly induces endothelial damage via the Gb3 receptor. Brain inflammation in STEC encephalopathies has been consistently reported and experimentally confirmed. The entry of Shiga toxin into the brain leads to direct neuronal damage through its interaction with neuronal Gb3, as demonstrated in clinical case studies and experimental models. This review also discusses the adverse effects of STEC on the brain, which may arise from metabolic or circulatory disruptions, secondary damage to the CNS, or a multifactorial combination. Recent studies have highlighted the significance of neuroimaging techniques in diagnosing HUS encephalopathy. Efforts have been made to identify early neural biomarkers and develop corresponding treatments. Although various biomarkers have been reported, additional studies are needed for further development and standardization. Late-stage pharmacological treatments for encephalopathy are also discussed, both in clinical settings and experimental research.