Human mAbs to Staphylococcus aureus IsdA Provide Protection Through Both Heme-Blocking and Fc-Mediated Mechanisms

摘要: The nutrient metal iron plays a key role in the survival of microorganisms. iron-regulated surface determinant (Isd) system scavenges heme-iron from human host, enabling acquisition iron-deplete conditions Staphylococcus aureus during infection. cell receptors IsdB and IsdH bind hemoproteins transfer heme to IsdA, final protein before is transported through peptidoglycan. To define B-cell response we isolated monoclonal antibodies (mAbs) specific Isd proteins determined their mechanism action. We describe first isolation fully IsdA mAbs, as well cross-reactive mAbs. Two identified mAbs worked murine septic model infection reduce bacterial burden staphylococcal Their protection was result both heme-blocking Fc-mediated effector functions, underscoring importance targeting S. using diverse mechanisms.