Therapeutic Strategies to Protect the Central Nervous System against Shiga Toxin from Enterohemorrhagic Escherichia coli

Infection with Shiga toxin-producing Escherichia coli (STEC) may cause hemorrhagic colitis, hemolytic uremic syndrome (HUS) and encephalopathy. The mortality rate derived from HUS adds up to 5% of the cases, and up to 40% when the central nervous system (CNS) is involved. In addition to the well-known deleterious effect of Stx, the gram-negative STEC releases lipopolysaccharides (LPS) and may induce a variety of inflammatory responses when released in the gut. Common clinical signs of severe CNS injury include sensorimotor, cognitive, emotional and/or autonomic alterations. In the last few years, a number of drugs have been experimentally employed to establish the pathogenesis of, prevent or treat CNS injury by STEC. The strategies in these approaches focus on: 1) inhibition of Stx production and release by STEC, 2) inhibition of Stx bloodstream transport, 3) inhibition of Stx entry into the CNS parenchyma, 4) blockade of deleterious Stx action in neural cells, and 5) inhibition of immune system activation and CNS inflammation. Fast diagnosis of STEC infection, as well as the establishment of early CNS biomarkers of damage, may be determinants of adequate neuropharmacological treatment in time.

Automated summary

Infection with Shiga toxin-producing Escherichia coli can result in hemorrhagic colitis, hemolytic uremic syndrome (HUS) and encephalopathy, with a high mortality rate when the central nervous system is involved. Recent research focuses on inhibiting Stx production and release, preventing Stx transport in the bloodstream, blocking Stx entry into the CNS, inhibiting Stx action in neural cells, and preventing immune system activation and CNS inflammation. Early diagnosis and establishment of CNS biomarkers are crucial for timely neuropharmacological treatment.