α and β chains of hemoglobin inhibit production of Staphylococcus aureus exotoxins

Prior studies suggest Staphylococcus aureus exotoxins are not produced when the organism is cultured in human blood. Human blood was fractionated into plasma and water-lysed red blood cells, and it was demonstrated that mixtures of α and β globins of hemoglobin (as low as 1 μg/mL) inhibited S. aureus exotoxin production while increasing production of protein A and not affecting bacterial growth. Pepsin but not trypsin digestion destroyed the ability of α and β globin to inhibit exotoxin production. Exotoxin production by both methicillin-resistant and methicillin-susceptible organisms was inhibited. Production of streptococcal pyrogenic exotoxin A by Streptococcus pyogenes was unaffected by α and β globin chains but was inhibited when produced in S. aureus. Use of isogenic S. aureus strains suggested the targets of α and β globin chains, leading to inhibition of staphylococcal exotoxins, included the two-component system SrrA-SrrB. δ hemolysin production was also inhibited, suggesting the two-component (and quorum sensing) system AgrA-AgrC was targeted. The α and β globin chains represent promising molecules to interfere with the pathogenesis of serious staphylococcal diseases.