Human hemoglobin as an iron source of Staphylococcus aureus

Abstract

MICROBIOLOGY AND IMMUNOLOGY

HUMAN HEMOGLOBIN AS AN IRON SOURCE OF STAPHYLOCOCCUS AUREUS

GLIB PISHCHANY

Dissertation under the direction of Professor Eric P. Skaar Staphylococcus aureus is a tremendous human pathogen that causes an array of life-threatening diseases. During invasive infection, S. aureus employs the iron regulated surface determinant (isd) system to bind and utilize host hemoglobin as a primary source of nutrient iron. We have found that surface anchored proteins of the Isd system co-localize within the cell wall. These results contribute to a mechanistic understanding of nutrient transport across the Gram positive cell wall. Further, we demonstrate that S. aureus has evolved to recognize human hemoglobin with improved efficiency compared to hemoglobin derived from other animal species. This evolutionary adaptation substantially contributes to pathogenicity, as revealed by an increased susceptibility to staphylococcal infection of transgenic mice expressing human hemoglobin. These results establish an improved animal model of systemic staphylococcal infection, and suggest that polymorphisms within human hemoglobin may affect individual susceptibility to S. aureus.