Evidence map›Paper›PMID 40876448›Full record

ArticleCell host & microbe2025

Cryptosporidium parvum multidrug resistance protein confers resistance to toxic gut microbial metabolite.

Wanyi Huang, Rui Xu, Abigail Kimball, William H Witola, Megan T Baldridge, Yaoyu Feng, Lihua Xiao, L David Sibley

Abstract read
In one paragraph

Article in Cell host & microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. New Cryptosporidium parvum fitness factor.Nature reviews. Microbiology · 2025
    Article
  6. Article
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

8 authors.

Wanyi HuangDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Rui XuDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Abigail KimballDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
William H WitolaDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802, USA.
Megan T BaldridgeDepartment of Medicine, Division of Infectious Diseases, Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Yaoyu FengState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Lihua XiaoState Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
L David SibleyDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: sibley@wustl.edu.

Funding

Effect of Microbial Metabolites on Growth of CryptosporidiumR01AI145496 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 2020 to 2023
$2.7M
Genetic Basis of Host Infectivity by CryptosporidiumR01AI175150 · NIAID · WASHINGTON UNIVERSITY · PI L. David Sibley · 2024 to 2026
$2.0M
NIAID NIH HHS R01 AI145496NIAID NIH HHS R01 AI175150
6 · The paper itself

Abstract

Cryptosporidium parvum subtypes differ in pathogenicity, but the underlying factors are largely unknown. We show that two genetically similar C. parvum isolates grow equally well in vitro but differ in pathogenicity in immunocompromised mice. Reduced oocyst shedding of the avirulent strain was restored by antibiotic treatment, suggesting susceptibility to colonization resistance imparted by the microbiota. This resistance was associated with a gene encoding a parasite ABC transporter and enhanced infectivity. Molecular analyses indicate that the ABC transporter belongs to a multidrug resistance protein (MRP) family. CpMRP1 binds bacterial metabolites, notably deoxycholic acid (DCA) that inhibits C. parvum growth. CpMRP1 is exported from small granules to the parasite-host interface, potentially mediating the export of xenobiotics. Loss of CpMRP1 reduces infectivity and DCA resistance in mice, and CpMRP1 polymorphisms across isolates determine susceptibility to DCA. These results define CpMRP1 as a determinant of C. parvum sensitivity to microbiome-mediated inhibition, thereby influencing infectivity.

Indexed as

ATP-Binding Cassette, Sub-Family C ProteinsCryptosporidium parvumGastrointestinal MicrobiomeProtozoan ProteinsAnimalsATP-Binding Cassette TransportersCryptosporidiosisDeoxycholic AcidHumansMiceOocystsVirulenceATP-Binding Cassette, Sub-Family C ProteinsATP-Binding Cassette TransportersDeoxycholic AcidProtozoan Proteinsbulk segregant analysisCryptosporidium parvumeffluximmunocompromisedmicrobial metabolitemicrobiotamultidrug resistance proteinpathogenicitypolymorphismvirulence determinant

Identifiers

PMID40876448
PMCPMC12477738

What OpenQuestion holds

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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.