The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
IsdA and IsdB antibodies protect mice against Staphylococcus aureus abscess formation and lethal challenge
Open accessAbstract
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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In the citing paper
“Consistent with the importance of heme-iron acquisition to the pathogenesis of staphylococcal infections, inactivation of isdA , isdB , isdC , isdG, or isdI reduces bacterial proliferation within the host [3, 4, 21, 27 -29].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [28]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In a separate study affinity-purified anti-IsdB antibodies administered to mice prior to intravenous challenge with S. aureus were found to significantly reduce the bacterial load and number of abscesses formed within the kidney [69].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [69]
In the citing paper
“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].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [117]
In the citing paper
“Mutation of isdA, isdB, and isdC, but not isdH, decreases bacterial recovery and organ abscesses in murine models of systemic infection [96, 116, 117].”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [117]
In the citing paper
“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.”
From Metal ion acquisition in Staphylococcus aureus: overcoming nutritional immunity (2012) · cites this paper as [117]
In the citing paper
“Moreover, antibodies against IsdA and IsdB rescue animals from lethal staphylococcal challenge and inhibit abscess formation (39).”
From Molecular Mechanisms of Staphylococcus aureus Iron Acquisition (2011) · cites this paper as [39]
In the citing paper
“Binding of hemoglobin and removal of heme are carried out in vitro by distinct domains within IsdB called NEAT1IsdB and NEAT2IsdB, respectively (Figure 1 B ) [5, 7, 18, 28, 30, 31].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [28]
In the citing paper
“NEAT1 IsdB is required and suffi cient to bind hemoglobin, whereas NEAT2IsdB is required and suf fi cient for heme binding [7, 28].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [28]
In the citing paper
“Because NEAT1 does not contribute to heme binding to IsdB, this effect is not due to a reduction in heme binding [28].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [28]
In the citing paper
“S. aureus strains lacking isdB are reduced for colonization in murine models of infection [3, 4, 27 -29].”
From IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus (2014) · cites this paper as [28]
In the citing paper
“Furthermore, passive immunization using IsdB-specific IgG significantly improved survival outcomes of mice infected with S. aureus [69].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [69]
In the citing paper
“Consistent with this, anti-IsdB antisera does not promote opsonization of S. aureus in mouse blood.”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [69]
In the citing paper
“Gram-positive bacteria are typically resistant to complement mediated lysis, therefore host clearance of S. aureus requires opsonophagocytic killing by immune cells [69].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [69]
In the citing paper
“A potential explanation for the protective effect of anti-IsdB antibodies was provided by the observation that affinity-purified rabbit antibodies directed against IsdB perturbed hemoglobin binding [69].”
From A battle for iron: host sequestration and Staphylococcus aureus acquisition (2012) · cites this paper as [69]
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Citations
Cites
1 retracted
Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues
Cheng, A. G., Kim, H. K., Burts, M. L., Krausz, T., Schneewind, O., & Missiakas, D. M. (2009) · The FASEB Journal · doi:10.1096/fj.09-135467 · Cited by 437
Self-citationRetractedStaphylococcus aureus Infections
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Staphylococcus aureus Sortase, an Enzyme that Anchors Surface Proteins to the Cell Wall
Mazmanian, S. K., Liu, G., Ton-That, H., & Schneewind, O. (1999) · Science · doi:10.1126/science.285.5428.760 · Cited by 1,053
Self-citationKlein, E. Y., Smith, D. L., & Laxminarayan, R. (2007) · Emerging infectious diseases · doi:10.3201/eid1312.070629 · Cited by 880
Current Knowledge of Type-Specific M Antigens of Group A Streptococci
Lancefield, R. C. (1962) · The Journal of Immunology · doi:10.4049/jimmunol.89.3.307 · Cited by 785
Staphylococcal Coagulase: Mode of Action and Antigenicity
Duthie, E. S., & Lorenz, L. (1952) · Microbiology · doi:10.1099/00221287-6-1-2-95 · Cited by 623
Passage of Heme-Iron Across the Envelope of Staphylococcus aureus
Mazmanian, S. K., Skaar, E. P., Gaspar, A. H., Humayun, M., Gornicki, P., Jelenska, J., Joachmiak, A., Missiakas, D. M., & Schneewind, O. (2003) · Science · doi:10.1126/science.1081147 · Cited by 593
Self-citationTon-That, H., Liu, G., Mazmanian, S. K., Faull, K. F., & Schneewind, O. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12424 · Cited by 567
Self-citationBaba, T., Bae, T., Schneewind, O., Takeuchi, F., & Hiramatsu, K. (2007) · Journal of Bacteriology · doi:10.1128/jb.01000-07 · Cited by 564
Self-citation
Cited by
Sorted by citations
Skeletal infections: microbial pathogenesis, immunity and clinical management
Masters, E. A., Ricciardi, B. F., Bentley, K. L. D. M., Moriarty, T. F., Schwarz, E. M., & Muthukrishnan, G. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00686-0 · Cited by 735
Nutritional immunity: the battle for nutrient metals at the host–pathogen interface
Murdoch, C. C., & Skaar, E. P. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00745-6 · Cited by 701
Molecular Mechanisms of Staphylococcus aureus Iron Acquisition
Hammer, N. D., & Skaar, E. P. (2011) · Annual Review of Microbiology · doi:10.1146/annurev-micro-090110-102851 · Cited by 379
Fowler, V. G., Allen, K. B., Moreira, E. D., Moustafa, M., Isgro, F., Boucher, H. W., Corey, G. R., Carmeli, Y., Betts, R. F., Hartzel, J. S., et al. (2013) · JAMA · doi:10.1001/jama.2013.3010 · Cited by 376
Recent developments in understanding the iron acquisition strategies of gram positive pathogens
Sheldon, J. R., & Heinrichs, D. E. (2015) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuv009 · Cited by 272
Metadata
- 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)
- PMC
- PMC3095377
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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