Evidence map›Paper›PMID 25025225›Full record

ArticlePloS one2014

Detecting novel genetic variants associated with isoniazid-resistant Mycobacterium tuberculosis.

Sandhya Shekar, Zhen Xuan Yeo, Joshua C L Wong, Maurice K L Chan, Danny C T Ong, Pumipat Tongyoo, Sin-Yew Wong, Ann S G Lee

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

8 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Deciphering Within-Host Microevolution ofMicrobiology and molecular biology reviews : MMBR · 2019
    Review
  5. Article
  6. Article
  7. Redefining MTBDRplus test results: what do indeterminate results actually mean?The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2016
    Article
  8. 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 at 2 institutions in 1 country.

Sandhya ShekarDivision of Medical Sciences, National Cancer Centre, Singapore, Singapore.
Zhen Xuan YeoDivision of Medical Sciences, National Cancer Centre, Singapore, Singapore.
Joshua C L WongDivision of Medical Sciences, National Cancer Centre, Singapore, Singapore.
Maurice K L ChanDivision of Medical Sciences, National Cancer Centre, Singapore, Singapore.
Danny C T OngDivision of Medical Sciences, National Cancer Centre, Singapore, Singapore.
Pumipat TongyooDivision of Medical Sciences, National Cancer Centre, Singapore, Singapore.
Sin-Yew WongDepartment of Infectious Diseases, Singapore General Hospital, Singapore, Singapore.
Ann S G LeeDivision of Medical Sciences, National Cancer Centre, Singapore, Singapore; Office of Clinical & Academic Faculty Affairs, Duke-NUS Graduate Medical School, Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
National Cancer Centre Singapore · SGSingapore General Hospital · SG

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIsoniazid (INH) is a highly effective antibiotic central for the treatment of Mycobacterium tuberculosis (MTB). INH-resistant MTB clinical isolates are frequently mutated in the katG gene and the inhA promoter region, but 10 to 37% of INH-resistant clinical isolates have no detectable alterations in currently known gene targets associated with INH-resistance. We aimed to identify novel genes associated with INH-resistance in these latter isolates. METHODOLOGY/PRINCIPAL

findingsINH-resistant clinical isolates of MTB were pre-screened for mutations in the katG, inhA, kasA and ndh genes and the regulatory regions of inhA and ahpC. Twelve INH-resistant isolates with no mutations, and 17 INH-susceptible MTB isolates were subjected to whole genome sequencing. Phylogenetically related variants and synonymous mutations were excluded and further analysis revealed mutations in 60 genes and 4 intergenic regions associated with INH-resistance. Sanger sequencing verification of 45 genes confirmed that mutations in 40 genes were observed only in INH-resistant isolates and not in INH-susceptible isolates. The ratios of non-synonymous to synonymous mutations (dN/dS ratio) for the INH-resistance associated mutations identified in this study were 1.234 for INH-resistant and 0.654 for INH-susceptible isolates, strongly suggesting that these mutations are indeed associated with INH-resistance.

conclusionThe discovery of novel targets associated with INH-resistance described in this study may potentially be important for the development of improved molecular detection strategies.

Indexed as

Antitubercular AgentsDrug Resistance, BacterialIsoniazidMutationMycobacterium tuberculosisPhylogenyPromoter Regions, GeneticAntitubercular AgentsIsoniazid

Identifiers

PMID25025225
PMCPMC4099304
OpenAlexW2027381728

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.