Evidence map›Paper›PMID 27203084›Full record

ArticlePloS one2016

Role of Alanine Dehydrogenase of Mycobacterium tuberculosis during Recovery from Hypoxic Nonreplicating Persistence.

Michelle M Giffin, Lanbo Shi, Maria L Gennaro, Charles D Sohaskey

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.9field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. CRISPR-Cas9-driven genome editing inFrontiers in microbiology · 2025
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Alanine synthesized by alanine dehydrogenase enables ammonium-tolerant nitrogen fixation inProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Understanding the Genetic Diversity ofFrontiers in genetics · 2022
    Article
  11. Review
  12. Article
  13. Targeting Non-ReplicatingInternational journal of molecular sciences · 2021
    Review
  14. Review
  15. Cell surface (Amsterdam, Netherlands) · 2021
    Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Alanine dehydrogenases in mycobacteria.Journal of microbiology (Seoul, Korea) · 2019
    Review
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

4 authors at 2 institutions in 1 country.

Michelle M GiffinDepartment of Veterans Affairs Medical Center, Long Beach, CA, United States of America.
Lanbo ShiPublic Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, United States of America.
Maria L GennaroPublic Health Research Institute, New Jersey Medical School, Rutgers University, Newark, NJ, United States of America.
Charles D SohaskeyDepartment of Veterans Affairs Medical Center, Long Beach, CA, United States of America.
Long Beach Medical Center · USRutgers, The State University of New Jersey · US

Funding

FISH-Flow platform for host-based tuberculosis diagnosticsR01AI104615 · NIAID · RBHS-NEW JERSEY MEDICAL SCHOOL · PI GENNARO, MARIA LAURA · 2013 to 2017
$5.5M
Mapping and modeling host-pathogen interactions in TB latency and reactivationR01HL106788 · NHLBI · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI BALAZSI, GABOR, GENNARO, MARIA LAURA · 2010 to 2013
$3.1M
NHLBI NIH HHS R01 HL106788NIAID NIH HHS R01 AI104615
6 · The paper itself

Abstract

Mycobacterium tuberculosis can maintain a nonreplicating persistent state in the host for decades, but must maintain the ability to efficiently reactivate and produce active disease to survive and spread in a population. Among the enzymes expressed during this dormancy is alanine dehydrogenase, which converts pyruvate to alanine, and glyoxylate to glycine concurrent with the oxidation of NADH to NAD. It is involved in the metabolic remodeling of M. tuberculosis through its possible interactions with both the glyoxylate and methylcitrate cycle. Both mRNA levels and enzymatic activities of isocitrate lyase, the first enzyme of the glyoxylate cycle, and alanine dehydrogenase increased during entry into nonreplicating persistence, while the gene and activity for the second enzyme of the glyoxylate cycle, malate synthase were not. This could suggest a shift in carbon flow away from the glyoxylate cycle and instead through alanine dehydrogenase. Expression of ald was also induced in vitro by other persistence-inducing stresses such as nitric oxide, and was expressed at high levels in vivo during the initial lung infection in mice. Enzyme activity was maintained during extended hypoxia even after transcription levels decreased. An ald knockout mutant of M. tuberculosis showed no reduction in anaerobic survival in vitro, but resulted in a significant lag in the resumption of growth after reoxygenation. During reactivation the ald mutant had an altered NADH/NAD ratio, and alanine dehydrogenase is proposed to maintain the optimal NADH/NAD ratio during anaerobiosis in preparation of eventual regrowth, and during the initial response during reoxygenation.

Indexed as

Alanine DehydrogenaseBacterial ProteinsGlyoxylatesMycobacterium tuberculosisNitric OxideOxidation-ReductionOxygenAlanine DehydrogenaseBacterial ProteinsGlyoxylatesglyoxylic acidNitric OxideOxygen

Identifiers

PMID27203084
PMCPMC4874671
OpenAlexW2405758942

What OpenQuestion holds

Textmetadata
LicenceCC0
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.