Immune evasion by Staphylococcus aureus conferred by iron-regulated surface determinant protein IsdH.
The ability of Staphylococcus aureus to avoid innate immune responses including neutrophil-mediated phagocytosis is crucial for the organism to cause infection. This multifactorial process involves several secreted and cell-surface-associated proteins. In this paper we report a novel mechanism of combating neutrophils that involves iron-regulated surface determinant protein H (IsdH). The IsdH protein is part of a complex that is only expressed under iron-restricted conditions in order to bind haemoglobin and extract and transport haem into the cytoplasm. A null mutant defective in expression of IsdH, and mutants expressing variants of IsdH with substitutions in residues predicted to be involved in ligand binding, were generated from S. aureus 8325-4. The IsdH-defective mutants were shown by several measures to have reduced virulence compared with the wild-type. The mutant was engulfed more rapidly by human neutrophils in the presence of serum opsonins, survived poorly in fresh whole human blood and was less virulent in a mouse model of sepsis. The protective mechanism seems to stem from an accelerated degradation of the serum opsonin C3b.
Visai
Livia
L
Center for Tissue Engineering, Via Ferrata 1, 27100 Pavia, Italy.|Department of Biochemistry, Viale Taramelli 3/b, 27100 Pavia, Italy.
Yanagisawa
Naoko
N
Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
Josefsson
Elisabet
E
Department of Rheumatology, University of Gothenburg, Gothenburg, Sweden.
Tarkowski
Andrej
A
Department of Rheumatology, University of Gothenburg, Gothenburg, Sweden.
Pezzali
Ilaria
I
Department of Biochemistry, Viale Taramelli 3/b, 27100 Pavia, Italy.
Rooijakkers
Suzan H M
SHM
Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Foster
Timothy J
TJ
Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland.
Speziale
Pietro
P
Department of Biochemistry, Viale Taramelli 3/b, 27100 Pavia, Italy.
D019943:Amino Acid Substitution; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003001:Cloning, Molecular; D003179:Complement C3b / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007501:Iron / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020125:Mutation, Missense; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology*; D010587:Phagocytosis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence
D000942:Antigens, Bacterial; C512792:IsdH protein, Staphylococcus aureus; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D003179:Complement C3b; D007501:Iron