Evidence map›Paper›PMID 35637331›Full record

ArticleNature microbiology2022

CRISPRi chemical genetics and comparative genomics identify genes mediating drug potency in Mycobacterium tuberculosis.

Shuqi Li, Nicholas C Poulton, Jesseon S Chang, Zachary A Azadian, Michael A DeJesus, Nadine Ruecker, Matthew D Zimmerman, Kathryn A Eckartt, Barbara Bosch, Curtis A Engelhart and 5 more

Open access · hybridAbstract read
In one paragraph

Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.

0numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed
20.6field-weighted citation impact, top 1% 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

160 citing papers in PubMed, 218 citations in OpenAlex.

  1. Article
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  18. Microbiology (Reading, England) · 2026
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  19. Article
  20. Cell wall remodeling-dependent morphotype switch inProceedings of the National Academy of Sciences of the United States of America · 2026
    Article

100 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Shuqi Li *Laboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, USA.
Nicholas C Poulton *Laboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, USA.
Jesseon S ChangLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0001-7767-1812
Zachary A AzadianLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, USA.
Michael A DeJesusLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, USA.
Nadine RueckerDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Matthew D ZimmermanCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
Kathryn A EckarttLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, USA.
Barbara BoschLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0001-7708-6461
Curtis A EngelhartDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-9324-5861
Daniel F SullivanDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-8326-9245
Martin GengenbacherCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
Véronique A DartoisCenter for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.ORCID http://orcid.org/0000-0001-9470-5009
Dirk SchnappingerDepartment of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0002-4445-7219
Jeremy M RockLaboratory of Host-Pathogen Biology, The Rockefeller University, New York, NY, USA. rock@rockefeller.edu.ORCID http://orcid.org/0000-0002-9310-951X
Rockefeller University · USCornell University · USHackensack Meridian Health · US

Funding

Towards a molecular understanding of persistent tuberculosis infectionDP2AI144850 · NIAID · ROCKEFELLER UNIVERSITY · PI ROCK, JEREMY MICHAEL · 2018 to 2018
$2.5M
A QTRAP 6500 LC-MS/MS System from SCIEX for high accuracy drug content analysisS10OD023524 · OD · RBHS-NEW JERSEY MEDICAL SCHOOL · PI DARTOIS, VERONIQUE · 2017 to 2017
$526k
NIAID NIH HHS DP2 AI144850NIH HHS S10 OD023524
6 · The paper itself

Abstract

Mycobacterium tuberculosis (Mtb) infection is notoriously difficult to treat. Treatment efficacy is limited by Mtb's intrinsic drug resistance, as well as its ability to evolve acquired resistance to all antituberculars in clinical use. A deeper understanding of the bacterial pathways that influence drug efficacy could facilitate the development of more effective therapies, identify new mechanisms of acquired resistance, and reveal overlooked therapeutic opportunities. Here we developed a CRISPR interference chemical-genetics platform to titrate the expression of Mtb genes and quantify bacterial fitness in the presence of different drugs. We discovered diverse mechanisms of intrinsic drug resistance, unveiling hundreds of potential targets for synergistic drug combinations. Combining chemical genetics with comparative genomics of Mtb clinical isolates, we further identified several previously unknown mechanisms of acquired drug resistance, one of which is associated with a multidrug-resistant tuberculosis outbreak in South America. Lastly, we found that the intrinsic resistance factor whiB7 was inactivated in an entire Mtb sublineage endemic to Southeast Asia, presenting an opportunity to potentially repurpose the macrolide antibiotic clarithromycin to treat tuberculosis. This chemical-genetic map provides a rich resource to understand drug efficacy in Mtb and guide future tuberculosis drug development and treatment.

Indexed as

Mycobacterium tuberculosisTuberculosisTuberculosis, Multidrug-ResistantAntitubercular AgentsGenomicsHumansAntitubercular Agents

Identifiers

PMID35637331
PMCPMC9159947
OpenAlexW4281631167

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.