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Cited by 65Yersinia bacterium, plague, ectoparasites researchBacillus and Francisella bacterial researchBacterial Infections and Vaccines

Hereditary Hemochromatosis Restores the Virulence of Plague Vaccine Strains

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Quenee, L. E., Hermanas, T. M., Ciletti, N., Louvel, H., Miller, N. C., Elli, D., Blaylock, B., Mitchell, A. +4 more·2012·Journal of Infectious Diseases
DOI 10.1093/infdis/jis433PMC PMC3501692
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Abstract

Nonpigmented Yersinia pestis (pgm) strains are defective in scavenging host iron and have been used in live-attenuated vaccines to combat plague epidemics. Recently, a Y. pestis pgm strain was isolated from a researcher with hereditary hemochromatosis who died from laboratory-acquired plague. We used hemojuvelin-knockout (Hjv(-/-)) mice to examine whether iron-storage disease restores the virulence defects of nonpigmented Y. pestis. Unlike wild-type mice, Hjv(-/-) mice developed lethal plague when challenged with Y. pestis pgm strains. Immunization of Hjv(-/-) mice with a subunit vaccine that blocks Y. pestis type III secretion generated protection against plague. Thus, individuals with hereditary hemochromatosis may be protected with subunit vaccines but should not be exposed to live-attenuated plague vaccines.

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  • Hepcidin-deficient mice are more susceptible than wild-type mice to death from infection with Y. enterocolitica and certain attenuated strains of Y. pestis.

    “Hepcidin-deficient mice are also much more susceptible than wild-type mice to death from infection with Y. enterocolitica (D. Stefanova, Y. Bulut, T.G. and E.N., unpublished observations) and certain attenuated strains of Y. pestis47.”

    From Iron homeostasis in host defence and inflammation (2015) · cites this paper as [47]

  • Pathogenicity of Y. pestis strains lacking yersiniabactin is greatly enhanced in haemochromatotic mice generated by disruption of hepcidin or haemojuvelin.

    “The pathogenicity of similar strains was greatly enhanced in haemochromatotic mice that were generated by disruption of the gene encoding either hepcidin or its essential regulator haemojuvelin47.”

    From Iron homeostasis in host defence and inflammation (2015) · cites this paper as [47]

  • People with hereditary hemochromatosis are highly susceptible to normally noninvasive microbes such as Vibrio vulnificus and Yersinia enterocolitica.

    “individuals with HH are highly susceptible to infection by normally noninvasive microbes, such as the bacteria Vibrio vulnificus and Yersinia enterocolitica 62, 63, 64.”

    From Buried Treasure: Evolutionary Perspectives on Microbial Iron Piracy (2015) · cites this paper as [63]

  • In mouse infection models, iron's importance has been supported for Vibrio vulnificus and nonpigmented Yersinia pestis plague vaccine strains.

    “The importance of iron has been corroborated in mouse models of infection by Vibrio vulnificus and nonpigmented Y. pestis (plague vaccine strains) (112, 146).”

    From Transition Metals and Virulence in Bacteria (2016) · cites this paper as [112]

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Cites

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Authors
Quenee, L. E., Hermanas, T. M., Ciletti, N., Louvel, H., Miller, N. C., Elli, D., Blaylock, B., Mitchell, A., Schroeder, J., Krausz, T., Kanabrocki, J., & Schneewind, O.
Affiliations
  • Argonne National Laboratory (US)
  • University of Chicago (US)
Corresponding author
Quenee, L. E.
ORCID
Schneewind, O.
Venue
Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2012-08-14
Volume
206
Issue
7
Pages
1050-1058
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1093/infdis/jis433
PMC
PMC3501692
OpenAlex
W2170242329
Cited by
65
References
7
Citations by year
2026: 2 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 5 · 2021: 12 · 2020: 3 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 7 · 2014: 3 · 2013: 2 · 2012: 1
FWCI
2.51
Type
journal article
Language
en
Open access
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (U54AI057153)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Yersinia bacterium, plague, ectoparasites research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacillus and Francisella bacterial research
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords
hereditary hemochromatosis, Yersinia pestis, plague, iron storage, iron acquisition, subunit vaccine, type III secretion system, vaccine safety
MeSH terms
Hemochromatosis Protein, Animals, Female, Hemochromatosis, Liver, Membrane Proteins, Plague, Plague Vaccine, Spleen, Vaccines, Attenuated, Virulence, Yersinia pestis, Mice, Knockout, Vaccines, Subunit, Microbial Viability, Mice, Mice, 129 Strain, GPI-Linked Proteins

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