1887

Abstract

The ability of 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 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.

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2009-03-01
2019-09-21
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