Cited by 158Antimicrobial Resistance in StaphylococcusBiochemical and Structural Characterizationvaccines and immunoinformatics approaches

IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge

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Kim, Hwan Keun, DeDent, Andrea, Cheng, Alice G., McAdow, Molly, Bagnoli, Fabio, Missiakas, Dominique M., Schneewind, Olaf·2010·Vaccine

Abstract

Staphylococcus aureus is the most frequent cause of bacteremia and hospital-acquired infection, however a vaccine that prevents staphylococcal disease is currently not available. Two sortase-anchored surface proteins, IsdA and IsdB, have been identified as subunit vaccines that, following active immunization, protect experimental animals against intravenous challenge with staphylococci. Here we investigate the molecular basis of this immunity and report that, when passively transferred to naïve mice, purified antibodies directed against IsdA or IsdB protected against staphylococcal abscess formation and lethal intravenous challenge. When added to mouse blood, IsdA- or IsdB-specific antibodies did not promote rapid opsonophagocytic killing of wild-type staphylococci. Antibodies directed against IsdA interfered with heme-binding and IsdB antibodies perturbed the ability of this surface protein to bind hemoglobin. As the structural genes for isdA and isdB are required for heme-iron scavenging during the pathogenesis of infection, we hypothesize that IsdA and IsdB antibodies may at least in part provide protection against staphylococci by interfering with the pathogen's heme-iron scavenging mechanisms.

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Crossref · 10.1016/j.vaccine.2010.02.097

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  • Examples include screening strategies to identify small-molecule inhibitors of FeoB, or antibodies that target IsdA and IsdB and prevent S. aureus from binding to haem, which has led to protection in mouse models of infection.

    “Examples include screening strategies to identify small- molecule inhibitors of FeoB 183-185 , or antibodies that target IsdA and IsdB and prevent S. aureus from binding to haem, which has led to protection in mouse models of infection 186,187 .”

    From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [187]

    The Abstract reports that antibodies against IsdA or IsdB protected mice from abscess formation and lethal challenge. Results §3.5 distinguishes their effects: anti-IsdA interfered with heme binding, while anti-IsdB blocked hemoglobin binding but did not reduce heme binding. The Discussion describes interference with heme-iron scavenging as a plausible, still speculative explanation for protection, not an established cause. Page numbers were not supplied. (LLM, conf=0.89)

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  • IsdA and IsdB were identified as vaccine candidates using reverse vaccinology, and immunization with these proteins is protective in murine models of infection.

    “IsdA and IsdB were identified as vaccine candidates using “reverse vaccinology” [119], and subsequent studies confirmed that immunization with these proteins is protective in murine models of infection [117, 120–123].”
  • Mutation of isdA, isdB, and isdC, but not isdH, decreases bacterial recovery and organ abscesses in murine models of systemic infection.

    “Mutation of isdA, isdB, and isdC, but not isdH, decreases bacterial recovery and organ abscesses in murine models of systemic infection [96, 116, 117].”
  • Disruption of the Isd heme acquisition system at each step leads to decreased virulence in animal models.

    “Several lines of evidence indicate that disruption of the Isd heme acquisition system at each step (surface receptor binding, transport across the cell wall, transport across the cell membrane, or release of iron from heme) leads to decreased virulence in animal models of staphylococcal infection.”
  • Antibodies against IsdA and IsdB rescue animals from lethal staphylococcal challenge and inhibit abscess formation.

    “Moreover, antibodies against IsdA and IsdB rescue animals from lethal staphylococcal challenge and inhibit abscess formation (39).”

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Authors
Kim, H. K., DeDent, A., Cheng, A. G., McAdow, M., Bagnoli, F., Missiakas, D. M., & Schneewind, O.
Affiliations
University of Chicago (US)
Corresponding author
Schneewind, Olaf
Venue
Vaccine
Publisher
Elsevier BV
Published
2010-08
Volume
28
Issue
38
Pages
6382-6392
ISSN
0264-410X (ISSN-L)
OpenAlex
W2163053334
Cited by
158
References
45
Citations by year
2026: 7 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 4 · 2018: 10 · 2017: 6 · 2016: 10 · 2015: 10 · 2014: 12 · 2013: 17 · 2012: 18
FWCI
11.98
Type
journal article
Language
en
Open access
Locations
  • Vaccine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (1ziahd009007-01)
  • National Institute of General Medical Sciences (T32GM007281, GM-07281)
  • National Institute of Allergy and Infectious Diseases (U54AI057153, AI52474, R01AI052474)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD009007)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
Staphylococcus aureus, ISDA, ISDB, passive antibody transfer, subunit vaccine, abscess formation, heme binding, hemoglobin binding, intravenous challenge, bacterial virulence factors
MeSH terms
Abscess, Animals, Antibodies, Bacterial, Antigens, Bacterial, Cross Reactions, Female, Heme, Hemoglobins, Humans, Immunization, Passive, Kidney, Mice, Inbred BALB C, Mutation, Rabbits, Staphylococcal Infections, Cation Transport Proteins, Mice

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