Fever temperatures impair hemolysis caused by strains of Escherichia coli and Staphylococcus aureus

Hemolysis modulates susceptibility to bacterial infections and predicts poor sepsis outcome. Hemolytic bacteria use hemolysins to induce erythrocyte lysis and obtain the heme that is essential for bacterial growth. Hemolysins are however potent immunogens and infections with hemolytic bacteria may cause a reversible fever response from the host that will aid in pathogen clearance. We hypothesized that fever temperatures impact the growth and infectivity of two hemolytic bacteria that are known to evoke fever in patients. To that end, we used high-sensitivity microcalorimetry to measure the evolution of heat production in fever-inducing strains of Escherichia coli and Staphylococcus aureus, under different temperature conditions. We determined specific bacterial aggregation profiles at temperatures equal to or exceeding 38.5 °C. Two melting temperatures peaks ranged from 38 °C to 43 °C for either species, a feature that we assigned to the formation of hemolysin aggregates of different oligomerization order. In order to measure the role of fever temperatures on hemolysis, we incubated the pathogens on blood agar plates at relevant temperatures, measuring the presence of hemolysis at 37 °C and its absence at 40.5 °C, respectively. We conclude that fever temperatures affect the kinetics of hemolysin pore formation and subsequently the hemolysis of red blood cells in vitro. We reveal the potential of microcalorimetry to monitor heat response from fever inducing bacterial species. Furthermore, these results help establish an additional positive role of febrile temperatures in modulating the immune response to infections, through the abolishment of hemolysis.