Hemolysin of uropathogenic Escherichia coli: A cloak or a dagger?

• UPEC hemolysin is associated with severe urinary tract infections.
• Intracellular calcium levels are affected following hemolysin intoxication.
• Sublytic effects of hemolysin can alter host cell regulation and lead to cell death.
• Comprehensive infection studies with various clinical isolates are warranted.
• As the RTX toxin family prototype, hemolysin studies will have broad implications.

Hemolysin from uropathogenic Escherichia coli (UPEC) is a hemolytic and cytotoxic protein active against a broad range of species and cell types. Expression of hemolysin correlates with severity of infection, as up to 78% of UPEC isolates from pyelonephritis cases express hemolysin. Despite decades of research on hemolysin activity, the mechanism of intoxication and the function of hemolysin in UPEC infection remain elusive. Early in vitro research established the role of hemolysin as a lytic protein at high doses. It is hypothesized that hemolysin is secreted at sublytic doses in vivo and recent research has focused on understanding the more subtle effects of hemolysin both in vitro and in elegant infection models in vivo, including inoculation by micropuncture of individual kidney nephrons. As the field continues to evolve, comparisons of hemolysin function in isolates from a range of UTI infections will be important for delineating the role of this toxin. This article is part of a Special Issue entitled: Pore-Forming Toxins edited by Mauro Dalla Serra and Franco Gambale.