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Cited by 54Clostridium difficile and Clostridium perfringens researchBacterial Genetics and BiotechnologyIron Metabolism and Disorders

Clostridioides difficile ferrosome organelles combat nutritional immunity

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Pi, Hualiang, Sun, Rong, McBride, James R., Kruse, Angela R. S., Gibson-Corley, Katherine N., Krystofiak, Evan S., Nicholson, Maribeth R., Spraggins, Jeffrey M. +2 more·2023·Nature
DOI 10.1038/s41586-023-06719-9PMC PMC10822667
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Abstract

Iron is indispensable for almost all forms of life but toxic at elevated levels 1-4. To survive within their hosts, bacterial pathogens have evolved iron uptake, storage and detoxification strategies to maintain iron homeostasis 1,5,6. Recent studies showed that three Gram-negative environmental anaerobes produce iron-containing ferrosome granules 7,8. However, it remains unclear whether ferrosomes are generated exclusively by Gram-negative bacteria. The Gram-positive bacterium Clostridioides difficile is the leading cause of nosocomial and antibiotic-associated infections in the USA 9. Here we report that C. difficile undergoes an intracellular iron biomineralization process and stores iron in membrane-bound ferrosome organelles containing non-crystalline iron phosphate biominerals. We found that a membrane protein (FezA) and a P 1B6-ATPase transporter (FezB), repressed by both iron and the ferric uptake regulator Fur, are required for ferrosome formation and play an important role in iron homeostasis during transition from iron deficiency to excess. Additionally, ferrosomes are often localized adjacent to cellular membranes as shown by cryo-electron tomography. Furthermore, using two mouse models of C. difficile infection, we demonstrated that the ferrosome system is activated in the inflamed gut to combat calprotectin-mediated iron sequestration and is important for bacterial colonization and survival during C. difficile infection.

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  • Iron may also be stored by loading into dedicated membrane-bound organelles known as ferrosomes, but their biology is only beginning to be understood.

    “Iron may also be stored by loading into dedicated membrane-bound organelles known as ferrosomes,134,135 but their biology is only beginning to be understood.”

    From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [134]

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Cited by

Sorted by citations

Authors
Pi, H., Sun, R., McBride, J. R., Kruse, A. R. S., Gibson-Corley, K. N., Krystofiak, E. S., Nicholson, M. R., Spraggins, J. M., Zhou, Q., & Skaar, E. P.
Affiliations
  • Vanderbilt University (US)
  • Vanderbilt University Medical Center (US)
Corresponding author
  • Zhou, Qiangjun
  • Skaar, Eric P.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2023-11-15
Volume
623
Issue
7989
Pages
1009-1016
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-023-06719-9
PMC
PMC10822667
OpenAlex
W4388694347
Cited by
54
References
12
Citations by year
2026: 13 · 2025: 20 · 2024: 20 · 2022: 1
FWCI
10.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Vanderbilt University (DK59637, DK20593, DK58404, CA68485, EY08126)
  • National Institutes of Health (1s10od030292-01, DK-59637, EY08126, CA68485, DK 20593, DK-58404, AI174999)
  • Vanderbilt Institute of Nanoscale Science and Engineering, Vanderbilt University
  • National Institute of Mental Health (R00MH113764)
  • National Eye Institute (P30EY008126)
  • National Cancer Institute (P30CA068485)
  • National Institute of Allergy and Infectious Diseases (K99AI168483, R00AI168483, F32AI161860, U19AI174999, R01AI164587, R01AI073843, R01AI138581, K23AI156132)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U24DK059637, P30DK058404, P30DK020593)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
Clostridium difficile, iron homeostasis, iron biomineralization, Fur repressor, nutritional immunity, calprotectin, intestinal colonization, Clostridium difficile infection, antimicrobial drug targets, cryo-electron tomography
MeSH terms
Host Microbial Interactions, Animals, Bacterial Proteins, Cell Membrane, Clostridium Infections, Disease Models, Animal, Ferric Compounds, Homeostasis, Inflammation, Intestines, Iron, Organelles, Clostridioides difficile, Cryoelectron Microscopy, Leukocyte L1 Antigen Complex, Microbial Viability, Mice, Electron Microscope Tomography

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