Evidence map›Paper›PMID 34549997›Full record

ArticleMicrobiology spectrum2021

The Human Innate Immune Protein Calprotectin Elicits a Multimetal Starvation Response in Pseudomonas aeruginosa.

Cassandra E Nelson, Weiliang Huang, Emily M Zygiel, Elizabeth M Nolan, Maureen A Kane, Amanda G Oglesby

Open access · goldAbstract read
In one paragraph

Article in Microbiology spectrum, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 23 citations in OpenAlex.

  1. Pseudogenization of the cntQ permease confers distinct yersinopine-metal uptake selectivity in Yersinia species.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Article
  2. Article
  3. Review
  4. Article
  5. Metal-independent effects of calprotectin on cocultures ofbioRxiv : the preprint server for biology · 2026
    Article
  6. Review
  7. Pseudopaline-mediated zinc uptake byInfection and immunity · 2026
    Article
  8. Article
  9. Calprotectin protectsmSystems · 2025
    Article
  10. Article
  11. Article
  12. Article
  13. mBio · 2024
    Article
  14. Article
  15. Nutrient Limitation SensitizesACS infectious diseases · 2023
    Article
  16. Targeting Skin Barrier Function in Atopic Dermatitis.The journal of allergy and clinical immunology. In practice · 2023
    Article
  17. Article
  18. Review
  19. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Cassandra E Nelson *Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimoregrid.411024.2, Baltimore, Maryland, USA.
Weiliang Huang *Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimoregrid.411024.2, Baltimore, Maryland, USA.
Emily M ZygielDepartment of Chemistry, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA.
Elizabeth M NolanDepartment of Chemistry, Massachusetts Institute of Technologygrid.116068.8, Cambridge, Massachusetts, USA.
Maureen A KaneDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimoregrid.411024.2, Baltimore, Maryland, USA.
Amanda G OglesbyDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimoregrid.411024.2, Baltimore, Maryland, USA.ORCID 0000-0003-4440-3840
University of Maryland, Baltimore · USMassachusetts Institute of Technology · US

Funding

Signaling Pathways in Innate ImmunityT32AI095190 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI Stefanie N. Vogel · 2012 to 2026
$4.7M
Metallobiochemistry of innate immunity and bacterial physiologyR01GM126376 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI NOLAN, ELIZABETH M, OGLESBY, AMANDA GAIL · 2017 to 2024
$2.4M
NIAID NIH HHS T32 AI095190NIGMS NIH HHS R01 GM126376
6 · The paper itself

Abstract

To combat infections, the mammalian host limits availability of essential transition metals such as iron (Fe), zinc (Zn), and manganese (Mn) in a strategy termed "nutritional immunity." The innate immune protein calprotectin (CP) contributes to nutritional immunity by sequestering these metals to exert antimicrobial activity against a broad range of microbial pathogens. One such pathogen is Pseudomonas aeruginosa, which causes opportunistic infections in vulnerable populations, including individuals with cystic fibrosis. CP was previously shown to withhold Fe(II) and Zn(II) from P. aeruginosa and induce Fe and Zn starvation responses in this pathogen. In this work, we performed quantitative, label-free proteomics to further elucidate how CP impacts metal homeostasis pathways in P. aeruginosa. We report that CP induces an incomplete Fe starvation response, as many Fe-containing proteins that are repressed by Fe limitation are not affected by CP treatment. The Zn starvation response elicited by CP seems to be more complete than the Fe starvation response and includes increases in Zn transporters and Zn-independent proteins. CP also induces the expression of membrane-modifying proteins, and metal depletion studies indicate this response results from the sequestration of multiple metals. Moreover, the increased expression of membrane-modifying enzymes upon CP treatment correlates with increased tolerance to polymyxin B. Thus, the response of P. aeruginosa to CP treatment includes both single- and multimetal starvation responses and includes many factors related to virulence potential, broadening our understanding of this pathogen's interaction with the host.

Indexed as

Immunity, InnateCarrier ProteinsCaseinsHomeostasisHumansIronLeukocyte L1 Antigen ComplexMicrobial Sensitivity TestsPeptide HydrolasesPolymyxin BPseudomonas aeruginosaVirulenceZincazocaseinCarrier ProteinsCaseinsIronLeukocyte L1 Antigen ComplexPeptide HydrolasesPolymyxin BZinczinc-binding proteincalprotectinironpolymyxin BproteasesPseudomonas aeruginosazinc

Identifiers

PMID34549997
PMCPMC8557868
OpenAlexW3159662346

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.