Cited by 36Bacterial Genetics and BiotechnologyIron Metabolism and DisordersBacterial biofilms and quorum sensing

Heme protects Pseudomonas aeruginosa and Staphylococcus aureus from calprotectin-induced iron starvation

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Zygiel, Emily M., Obisesan, Adunoluwa O., Nelson, Cassandra E., Oglesby, Amanda G., Nolan, Elizabeth M.·2021·Journal of Biological Chemistry

Abstract

Pseudomonas aeruginosa and Staphylococcus aureus are opportunistic bacterial pathogens that cause severe infections in immunocompromised individuals and patients with cystic fibrosis. Both P. aeruginosa and S. aureus require iron to infect the mammalian host. To obtain iron, these pathogens may rely on siderophore-mediated ferric iron uptake, ferrous iron uptake, or heme uptake at different points during infection. The preferred iron source depends on environmental conditions, including the presence of iron-sequestering host-defense proteins. Here, we investigate how the presence of heme, a highly relevant iron source during infection, affects bacterial responses to iron withholding by the innate immune protein calprotectin (CP). Prior work has shown that P. aeruginosa is starved of iron in the presence of CP. We report that P. aeruginosa upregulates expression of heme uptake machinery in response to CP. Furthermore, we show that heme protects P. aeruginosa from CP-mediated inhibition of iron uptake and iron-starvation responses. We extend our study to a second bacterial pathogen, S. aureus, and demonstrate that CP also inhibits iron uptake and induces iron-starvation responses by this pathogen. Similarly to P. aeruginosa, we show that heme protects S. aureus from CP-mediated inhibition of iron uptake and iron-starvation responses. These findings expand our understanding of microbial responses to iron sequestration by CP and highlight the importance of heme utilization for bacterial adaptation to host iron-withholding strategies.

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Crossref · 10.1074/jbc.ra120.015975

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  • In the presence of the Fe-sequestering protein calprotectin, haem availability is essential for the survival of Staphylococcus aureus and Pseudomonas aeruginosa, highlighting the importance of haem as an Fe source within the host.

    “For instance, in the presence of the Fe- sequestering protein calprotectin, haem availability is essential for the survival of S. aureus and Pseudomonas aeruginosa , highlighting the importance of haem as an Fe source within the host 41 .”

    From Nutritional immunity: the battle for nutrient metals at the host–pathogen interface (2022) · cites this paper as [41]

    The Results and Discussion report that haem protects both species from calprotectin-induced iron depletion and starvation. They do not establish that haem is essential for their survival in the presence of calprotectin; the Discussion describes its protective role during infection as a possibility, not a demonstrated host finding. (LLM, conf=0.88)

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Authors
Zygiel, E. M., Obisesan, A. O., Nelson, C. E., Oglesby, A. G., & Nolan, E. M.
Affiliations
  • Massachusetts Institute of Technology (US)
  • University of Maryland, Baltimore (US)
Corresponding author
  • Oglesby, Amanda G.
  • Nolan, Elizabeth M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2021-01
Volume
296
Pages
100160
ISSN
0021-9258 (ISSN-L)
OpenAlex
W3109184006
Cited by
36
References
63
Citations by year
2026: 10 · 2025: 6 · 2024: 6 · 2023: 5 · 2022: 6 · 2021: 3
FWCI
2.05
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Keywords
heme uptake, calprotectin, iron starvation, Pseudomonas aeruginosa, Staphylococcus aureus, iron sequestration, innate immunity, bacterial iron acquisition, host-pathogen interaction, iron starvation response, siderophores, ferrous iron uptake
MeSH terms
Adaptation, Physiological, Bacterial Proteins, Binding, Competitive, Carrier Proteins, Heme, Humans, Iron, Protein Binding, Pseudomonas aeruginosa, Staphylococcus aureus, Stress, Physiological, Gene Expression Regulation, Bacterial, Siderophores, Leukocyte L1 Antigen Complex, Host-Pathogen Interactions, Bacterial Load

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