Evidence map›Paper›PMID 37405387›Full record

ArticleG3 (Bethesda, Md.)2023

Genome-wide screen identifies host loci that modulate Mycobacterium tuberculosis fitness in immunodivergent mice.

Rachel K Meade, Jarukit E Long, Adrian Jinich, Kyu Y Rhee, David G Ashbrook, Robert W Williams, Christopher M Sassetti, Clare M Smith

Open access · goldAbstract read
In one paragraph

Article in G3 (Bethesda, Md.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

11 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Article
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  4. Article
  5. Article
  6. Review
  7. Review
  8. Journal of bacteriology · 2025
    Article
  9. Review
  10. Review
  11. Inhibitors of the Thioesterase Activity ofACS infectious diseases · 2024
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

Rachel K MeadeDepartment of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
Jarukit E LongDepartment of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, MA 01655, USA.
Adrian JinichDivision of Infectious Diseases, Weill Cornell Medical College, New York, NY 10021, USA.
Kyu Y RheeDivision of Infectious Diseases, Weill Cornell Medical College, New York, NY 10021, USA.
David G AshbrookDepartment of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Robert W WilliamsDepartment of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Christopher M SassettiDepartment of Microbiology and Physiological Systems, UMass Chan Medical School, Worcester, MA 01655, USA.
Clare M SmithDepartment of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
Cornell University · USDuke University · USUniversity of Tennessee Health Science Center · USCharles River Laboratories (United States) · USUniversity of Massachusetts Chan Medical School · US

Funding

Regional Biocontainment Laboratory (RBL)UC6AI058607 · NIAID · DUKE UNIVERSITY · PI WILLIAMS, R SANDERS · 2003 to 2005
$16.3M
Systems Genetics of TuberculosisP01AI132130 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI PARDO-MANUEL DE VILLENA, FERNANDO · 2017 to 2021
$11.2M
Regional Biocontainment Laboratories Facility and Building System Upgrades SupportG20AI167200 · NIAID · DUKE UNIVERSITY · PI STAATS, HERMAN F · 2021 to 2022
$6.6M
A Unified High Performance Web Service for Systems Genetics and Precision MedicineR01GM123489 · NIGMS · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI PRINS, PJOTR, SEN, SAUNAK · 2017 to 2024
$3.7M
Genetics and Genomics Training GrantT32GM136627 · NIGMS · DUKE UNIVERSITY · PI ALLISON E ASHLEY-KOCH · 2020 to 2026
$3.1M
Dissecting the genetic basis of protective immunity to tuberculosis in diverse hostsDP2GM146458 · NIGMS · DUKE UNIVERSITY · PI SMITH, CLARE MARGARET · 2021 to 2021
$1.4M
Dissecting the genetic basis of protective immunity to tuberculosis in diverse hostsDP2AI183152 · NIAID · DUKE UNIVERSITY · PI SMITH, CLARE MARGARET · 2024 to 2024
$966k
NIAID NIH HHS DP2 AI183152NIAID NIH HHS G20 AI167200NIAID NIH HHS P01 AI132130NIAID NIH HHS UC6 AI058607NIGMS NIH HHS DP2 GM146458NIGMS NIH HHS R01 GM123489NIGMS NIH HHS T32 GM136627
6 · The paper itself

Abstract

Genetic differences among mammalian hosts and among strains of Mycobacterium tuberculosis (Mtb) are well-established determinants of tuberculosis (TB) patient outcomes. The advent of recombinant inbred mouse panels and next-generation transposon mutagenesis and sequencing approaches has enabled dissection of complex host-pathogen interactions. To identify host and pathogen genetic determinants of Mtb pathogenesis, we infected members of the highly diverse BXD family of strains with a comprehensive library of Mtb transposon mutants (TnSeq). Members of the BXD family segregate for Mtb-resistant C57BL/6J (B6 or B) and Mtb-susceptible DBA/2J (D2 or D) haplotypes. The survival of each bacterial mutant was quantified within each BXD host, and we identified those bacterial genes that were differentially required for Mtb fitness across BXD genotypes. Mutants that varied in survival among the host family of strains were leveraged as reporters of "endophenotypes," each bacterial fitness profile directly probing specific components of the infection microenvironment. We conducted quantitative trait loci (QTL) mapping of these bacterial fitness endophenotypes and identified 140 host-pathogen QTL (hpQTL). We located a QTL hotspot on chromosome 6 (75.97-88.58 Mb) associated with the genetic requirement of multiple Mtb genes: Rv0127 (mak), Rv0359 (rip2), Rv0955 (perM), and Rv3849 (espR). Together, this screen reinforces the utility of bacterial mutant libraries as precise reporters of the host immunological microenvironment during infection and highlights specific host-pathogen genetic interactions for further investigation. To enable downstream follow-up for both bacterial and mammalian genetic research communities, all bacterial fitness profiles have been deposited into GeneNetwork.org and added into the comprehensive collection of TnSeq libraries in MtbTnDB.

Indexed as

Mycobacterium tuberculosisAnimalsMammalsMiceMice, Inbred C57BLMice, Inbred DBAMutagenesisQuantitative Trait Locibacterial geneticsBXDcomplex traitsgenetic diversitygenomicshost–pathogen interactionsmouse modelsmycobacterianatural variationQTL mappingsystems geneticsTnSeqtuberculosis

Identifiers

PMID37405387
PMCPMC10468300
OpenAlexW4383186451

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.