Alpha and Beta Chains of Hemoglobin Inhibit Production of Staphylococcus Aureus Exotoxins

Biochemistry. 2007 Dec 18;46(50):14349-58. doi: 10.1021/bi701202w. Epub 2007 Nov 20.

Abstract

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 alpha and beta globins of hemoglobin (as low as 1 mug/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 alpha and beta 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 alpha and beta globin chains but was inhibited when produced in S. aureus. Use of isogenic S. aureus strains suggested the targets of alpha and beta globin chains, leading to inhibition of staphylococcal exotoxins, included the two-component system SrrA-SrrB. delta hemolysin production was also inhibited, suggesting the two-component (and quorum sensing) system AgrA-AgrC was targeted. The alpha and beta globin chains represent promising molecules to interfere with the pathogenesis of serious staphylococcal diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Toxins / metabolism
  • Blotting, Western
  • Chromatography, High Pressure Liquid
  • Enterotoxins / metabolism
  • Erythrocytes / microbiology
  • Exotoxins / metabolism*
  • Globins / chemistry
  • Globins / isolation & purification
  • Globins / pharmacology
  • Hemoglobins / chemistry
  • Hemoglobins / isolation & purification
  • Hemoglobins / pharmacology*
  • Hemolysin Proteins / metabolism
  • Humans
  • Isoelectric Focusing
  • Lipase / metabolism
  • Methicillin Resistance
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / metabolism*
  • Superantigens / metabolism

Substances

  • Bacterial Toxins
  • Enterotoxins
  • Exotoxins
  • Hemoglobins
  • Hemolysin Proteins
  • Superantigens
  • enterotoxin F, Staphylococcal
  • Globins
  • Lipase