Evidence map›Paper›PMID 40404665›Full record

ArticleNPJ vaccines2025

TnSeq identifies genetic requirements of Mycobacterium tuberculosis for survival under vaccine-induced immunity.

Kimra S James, Neharika Jain, Kelly Witzl, Nico Cicchetti, Sarah M Fortune, Thomas R Ioerger, Amanda J Martinot, Allison F Carey

Abstract read
In one paragraph

Article in NPJ vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Mce transport systems inJournal of bacteriology · 2026
    Review
  3. EliminateJournal of medical microbiology · 2026
    Article
  4. 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.

Kimra S JamesDivision of Microbiology & Immunology, Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Neharika JainDepartment of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, USA.
Kelly WitzlDivision of Microbiology & Immunology, Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Nico CicchettiDivision of Microbiology & Immunology, Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Sarah M FortuneDepartment of Immunology & Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Thomas R IoergerDepartment of Computer Science and Engineering, Texas A&M University, College Station, TX, USA.
Amanda J MartinotDepartment of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, MA, USA. amanda.martinot@tufts.edu.
Allison F CareyDivision of Microbiology & Immunology, Department of Pathology, University of Utah, Salt Lake City, UT, USA. allison.carey@path.utah.edu.

Funding

Resources and workforce development for the New England Regional Biosafety LaboratoryUC7AI180310 · NIAID · TUFTS UNIVERSITY BOSTON · PI Cheryl A London, Sam R Telford · 2023 to 2026
$11.8M
Systems Genetics of TuberculosisP01AI132130 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BEHAR, SAMUEL M · 2017 to 2021
$11.2M
Parallel phenotyping to dissect genetic determinants of bacterial strain diversityDP2AI171122 · NIAID · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Allison Carey · 2022 to 2026
$2.4M
Mycobacterial determinants of escape from pathogen-specific immunityK08AI139339 · NIAID · UNIVERSITY OF UTAH · PI CAREY, ALLISON · 2018 to 2022
$1.0M
High-Throughput TB Vaccine Antigen DiscoveryK08AI135098 · NIAID · TUFTS UNIVERSITY BOSTON · PI MARTINOT, AMANDA · 2018 to 2022
$931k
NIAID NIH HHS DP2 AI171122NIAID NIH HHS K08 AI135098NIAID NIH HHS K08 AI139339NIAID NIH HHS L70 AI178785NIAID NIH HHS P01 AI132130NIAID NIH HHS UC7 AI180310NIH HHS DP2 AI171122-S1NIH HHS K08 AI135098NIH HHS K08 AI139339NIH HHS P01 AI132130
6 · The paper itself

Abstract

Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB), remains a persistent global health challenge due to the lack of an effective vaccine. The only licensed TB vaccine, Bacille Calmette-Guerin (BCG), is a live attenuated strain of Mycobacterium bovis that protects young children from severe disease but fails to provide protection through adulthood. It is unclear why BCG provides incomplete protection despite inducing a robust Th1 immune response. We set out to interrogate mycobacterial determinants of vaccine escape using a functional genomics approach, TnSeq, to define bacterial genes required for survival in mice vaccinated with BCG, the live attenuated Mtb vaccine strain, ΔLprG, and in mice with Mtb immunity conferred by prior infection. We find that critical virulence genes associated with acute infection and exponential growth are less essential in hosts with adaptive immunity, including genes encoding the Esx-1 and Mce1 systems. Genetic requirements for Mtb growth in vaccinated and previously Mtb-infected hosts mirror the genetic requirements reported for bacteria under in vitro conditions that reflect aspects of the adaptive immune response. Across distinct immunization conditions, differences in genetic requirements between live attenuated vaccines and vaccination routes are observed, suggesting that different immunization strategies impose distinct bacterial stressors. Collectively, these data support the idea that Mtb requires genes that enable stress adaptation and growth arrest upon encountering the restrictive host environment induced by the adaptive immune response. We demonstrate that TnSeq can be used to understand the bacterial genetic requirements for survival in vaccinated hosts across pre-clinical live attenuated vaccines and therefore may be applied to other vaccine modalities. Understanding how Mtb survives vaccine-induced immunity has the potential to inform the development of new vaccines or adjuvant therapies.

Identifiers

PMID40404665
PMCPMC12098976

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Registered trials

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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.