title: Alpha and beta chains of hemoglobin inhibit production of Staphylococcus aureus exotoxins.
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.
authors.affiliation: Department of Microbiology, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, Minnesota 55455, USA. schli001@umn.edu
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Schlievert
authors.forename: Laura C
authors.initials: LC
authors.lastname: Case
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Nemeth
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Davis
authors.forename: Yiping
authors.initials: Y
authors.lastname: Sun
authors.forename: Wendy
authors.initials: W
authors.lastname: Qin
authors.forename: Fancheng
authors.initials: F
authors.lastname: Wang
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Brosnahan
authors.forename: John A
authors.initials: JA
authors.lastname: Mleziva
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Peterson
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Jones
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004768:Enterotoxins / Q000378:metabolism; D004912:Erythrocytes / Q000382:microbiology; D005098:Exotoxins / Q000378:metabolism*; D005914:Globins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006454:Hemoglobins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006460:Hemolysin Proteins / Q000378:metabolism; D006801:Humans; D007525:Isoelectric Focusing; D008049:Lipase / Q000378:metabolism; D016106:Methicillin Resistance; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000378:metabolism*; D018089:Superantigens / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D006454:Hemoglobins; D006460:Hemolysin Proteins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D005914:Globins; D008049:Lipase