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

Livia Visai^1,2,

Naoko Yanagisawa^3,

Andrej Tarkowski^4,

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.

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.