Immune evasion by Staphylococcus aureus conferred by iron-regulated surface determinant protein IsdH

• Published in: Microbiology (Society for General Microbiology) 2009-03, Vol.155 (3), p.667-679
• Main Authors: Visai, Livia, Yanagisawa, Naoko, Josefsson, Elisabet, Tarkowski, Andrej, Pezzali, Ilaria, Rooijakkers, Suzan H. M, Foster, Timothy J, Speziale, Pietro
• Format: Article
• Language: English
• Subjects: adhesin; Amino Acid Substitution; Animals; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Antigens, Bacterial - metabolism; Bacteriology; Biological and medical sciences; Cloning, Molecular; Complement C3b - immunology; Disease Models, Animal; Female; Fundamental and applied biological sciences. Psychology; Humans; Iron - immunology; Iron - metabolism; Mice; Microbiology; Microbiology in the medical area; Mikrobiologi inom det medicinska området; Miscellaneous; Mutation, Missense; Neutrophils - immunology; Neutrophils - microbiology; Phagocytosis; Receptors, Cell Surface - genetics; Receptors, Cell Surface - immunology; Receptors, Cell Surface - metabolism; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; sepsis; Staphylococcal Infections - immunology; Staphylococcal Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - immunology; Staphylococcus aureus - metabolism; Staphylococcus aureus - pathogenicity; Virulence; virulens
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.025684-0

1 Department of Biochemistry, Viale Taramelli 3/b, 27100 Pavia, Italy 2 Center for Tissue Engineering, Via Ferrata 1, 27100 Pavia, Italy 3 Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin 2, Ireland 4 Department of Rheumatology, University of Gothenburg, Gothenburg, Sweden 5 Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands Correspondence Timothy J. Foster tfoster{at}tcd.ie 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. Abbreviations: GST, glutathione S -transferase; Hp–Hb, haptoglobin–haemoglobin; HRP, horseradish peroxidase; NEAT motif, NEAr Transporter motif; NHS, normal human serum; PMNL, polymorphonuclear leukocytes These authors contributed equally to this work. This paper is dedicated to the memory of Andrej Tarkowski, who passed away tragically on 1 June 2008.