James Crowe
Faculty Member
Last active: 3/31/2020

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

Bennett MR, Bombardi RG, Kose N, Parrish EH, Nagel MB, Petit RA, Read TD, Schey KL, Thomsen IP, Skaar EP, Crowe JE
J Infect Dis. 2019 219 (8): 1264-1273

PMID: 30496483 · PMCID: PMC6452300 · DOI:10.1093/infdis/jiy635

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

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

MeSH Terms (14)

Animals Antibodies, Monoclonal Antigens, Bacterial Bacterial Proteins Disease Models, Animal Female Hemeproteins Humans Hydrogen Deuterium Exchange-Mass Spectrometry Mice Mice, Inbred BALB C Receptors, Cell Surface Staphylococcal Infections Staphylococcus aureus

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