Evidence map›Paper›PMID 35427399›Full record

ArticlePLoS pathogens2022

Mycobacterium tuberculosis requires SufT for Fe-S cluster maturation, metabolism, and survival in vivo.

Ashutosh Tripathi, Kushi Anand, Mayashree Das, Ruchika Annie O'Niel, Sabarinath P S, Chandrani Thakur, Raghunatha Reddy R L, Raju S Rajmani, Nagasuma Chandra, Sunil Laxman and 1 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Recent Characterization of Key Proteins to Combat Tuberculosis.Advances in experimental medicine and biology · 2026
    Review
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Genome mining ofFrontiers in microbiology · 2024
    Article
  13. Article
  14. Article
  15. TheMicroorganisms · 2023
    Article
  16. 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

11 authors.

Ashutosh TripathiCentre for Infectious Disease Research (CIDR), Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru, India.
Kushi AnandCentre for Infectious Disease Research (CIDR), Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru, India.
Mayashree DasCentre for Infectious Disease Research (CIDR), Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru, India.
Ruchika Annie O'NielInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, India.
Sabarinath P SInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, India.
Chandrani ThakurDepartment of Biochemistry, Indian Institute of Science, Bangalore, India.
Raghunatha Reddy R LRegional Horticultural Research and Extension Centre (RHREK), GKVK, Bengaluru, India.
Raju S RajmaniCentre for Infectious Disease Research (CIDR), Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru, India.
Nagasuma ChandraDepartment of Biochemistry, Indian Institute of Science, Bangalore, India.
Sunil LaxmanInstitute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, India.
Amit SinghCentre for Infectious Disease Research (CIDR), Department of Microbiology and Cell Biology, Indian Institute of Science (IISc), Bengaluru, India.ORCID 0000-0001-6761-1664

Funding

DBT-Wellcome Trust India Alliance IA/S/16/2/502700
6 · The paper itself

Abstract

Iron-sulfur (Fe-S) cluster proteins carry out essential cellular functions in diverse organisms, including the human pathogen Mycobacterium tuberculosis (Mtb). The mechanisms underlying Fe-S cluster biogenesis are poorly defined in Mtb. Here, we show that Mtb SufT (Rv1466), a DUF59 domain-containing essential protein, is required for the Fe-S cluster maturation. Mtb SufT homodimerizes and interacts with Fe-S cluster biogenesis proteins; SufS and SufU. SufT also interacts with the 4Fe-4S cluster containing proteins; aconitase and SufR. Importantly, a hyperactive cysteine in the DUF59 domain mediates interaction of SufT with SufS, SufU, aconitase, and SufR. We efficiently repressed the expression of SufT to generate a SufT knock-down strain in Mtb (SufT-KD) using CRISPR interference. Depleting SufT reduces aconitase's enzymatic activity under standard growth conditions and in response to oxidative stress and iron limitation. The SufT-KD strain exhibited defective growth and an altered pool of tricarboxylic acid cycle intermediates, amino acids, and sulfur metabolites. Using Seahorse Extracellular Flux analyzer, we demonstrated that SufT depletion diminishes glycolytic rate and oxidative phosphorylation in Mtb. The SufT-KD strain showed defective survival upon exposure to oxidative stress and nitric oxide. Lastly, SufT depletion reduced the survival of Mtb in macrophages and attenuated the ability of Mtb to persist in mice. Altogether, SufT assists in Fe-S cluster maturation and couples this process to bioenergetics of Mtb for survival under low and high demand for Fe-S clusters.

Indexed as

Iron-Sulfur ProteinsMycobacterium tuberculosisAconitate HydrataseAnimalsBacterial ProteinsIronMiceSulfurTranscription FactorsAconitate HydrataseBacterial ProteinsIronIron-Sulfur ProteinsSulfurTranscription Factors

Identifiers

PMID35427399
PMCPMC9045647

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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.