Human mAbs to Staphylococcus aureus IsdA Provide Protection Through Both Heme-Blocking and Fc-Mediated Mechanisms.
Animals
Antibodies, Monoclonal
/ immunology
Antigens, Bacterial
/ immunology
Bacterial Proteins
Disease Models, Animal
Female
Hemeproteins
/ immunology
Humans
Hydrogen Deuterium Exchange-Mass Spectrometry
Mice
Mice, Inbred BALB C
Receptors, Cell Surface
/ immunology
Staphylococcal Infections
/ immunology
Staphylococcus aureus
/ immunology
Staphyloccocus aureus
IsdA
NEAr iron transporter
antibodies
human
iron-regulated surface determinant system
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
08 04 2019
08 04 2019
Historique:
received:
11
09
2018
accepted:
17
11
2018
pubmed:
30
11
2018
medline:
9
1
2020
entrez:
30
11
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30496483
pii: 5218956
doi: 10.1093/infdis/jiy635
pmc: PMC6452300
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antigens, Bacterial
0
Bacterial Proteins
0
Hemeproteins
0
IsdA protein, Staphylococcus aureus
0
IsdH protein, Staphylococcus aureus
0
Receptors, Cell Surface
0
CRM197 (non-toxic variant of diphtheria toxin)
08VC9WC084
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1264-1273Subventions
Organisme : NIAID NIH HHS
ID : K23 AI113150
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI069233
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI073843
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI112541
Pays : United States
Informations de copyright
© 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.
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