Evidence map›Paper›PMID 29567948›Full record

ArticleScientific reports2018

Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae.

Sundeep Chaitanya Vedithi, Sony Malhotra, Madhusmita Das, Sheela Daniel, Nanda Kishore, Anuja George, Shantha Arumugam, Lakshmi Rajan, Mannam Ebenezer, David B Ascher and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
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  16. Distinguishing between PTEN clinical phenotypes through mutation analysis.Computational and structural biotechnology journal · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 4 countries.

Sundeep Chaitanya VedithiDepartment of Biochemistry, University of Cambridge, Tennis Court Rd., Cambridge, CB2 1GA, UK. scv26@cam.ac.uk.
Sony MalhotraDepartment of Biochemistry, University of Cambridge, Tennis Court Rd., Cambridge, CB2 1GA, UK.
Madhusmita DasMolecular Biology and Immunology Division, Schieffelin Institute of Health Research & Leprosy Center (SIH R & LC), Karigiri, Vellore, Tamil Nadu, 632106, India.
Sheela DanielMolecular Biology and Immunology Division, Schieffelin Institute of Health Research & Leprosy Center (SIH R & LC), Karigiri, Vellore, Tamil Nadu, 632106, India.
Nanda KishoreDepartment of Dermatology, Father Muller Medical College & Hospital, Mangalore, Karnataka, 575 002, India.
Anuja GeorgeDepartment of Dermatology, Trivandrum Medical College, Trivandrum, Kerala, 695011, India.
Shantha ArumugamMolecular Biology and Immunology Division, Schieffelin Institute of Health Research & Leprosy Center (SIH R & LC), Karigiri, Vellore, Tamil Nadu, 632106, India.
Lakshmi RajanMolecular Biology and Immunology Division, Schieffelin Institute of Health Research & Leprosy Center (SIH R & LC), Karigiri, Vellore, Tamil Nadu, 632106, India.
Mannam EbenezerMolecular Biology and Immunology Division, Schieffelin Institute of Health Research & Leprosy Center (SIH R & LC), Karigiri, Vellore, Tamil Nadu, 632106, India.
David B AscherDepartment of Biochemistry and Molecular Biology, Bio21 Institute, University of Melbourne, Parkville, VIC 3052, Australia.
Eddy ArnoldCenter for Advanced Biotechnology and Medicine (CABM), and Rutgers University Department of Chemistry and Chemical Biology, 679 Hoes Lane, Piscataway, NJ, 08854, USA.
Tom L BlundellDepartment of Biochemistry, University of Cambridge, Tennis Court Rd., Cambridge, CB2 1GA, UK. tlb20@cam.ac.uk.ORCID 0000-0002-2708-8992
Schieffelin Institute of Health Research and Leprosy Centre · INUniversity of Cambridge · GBFather Muller Medical College Hospital · INRutgers, The State University of New Jersey · USThe University of Melbourne · AU

Funding

Medical Research Council MR/M026302/1Medical Research Council RG78439Wellcome TrustWellcome Trust 200814/Z/16/Z
6 · The paper itself

Abstract

The rpoB gene encodes the β subunit of RNA polymerase holoenzyme in Mycobacterium leprae (M. leprae). Missense mutations in the rpoB gene were identified as etiological factors for rifampin resistance in leprosy. In the present study, we identified mutations corresponding to rifampin resistance in relapsed leprosy cases from three hospitals in southern India which treat leprosy patients. DNA was extracted from skin biopsies of 35 relapse/multidrug therapy non-respondent leprosy cases, and PCR was performed to amplify the 276 bp rifampin resistance-determining region of the rpoB gene. PCR products were sequenced, and mutations were identified in four out of the 35 cases at codon positions D441Y, D441V, S437L and H476R. The structural and functional effects of these mutations were assessed in the context of three-dimensional comparative models of wild-type and mutant M. leprae RNA polymerase holoenzyme (RNAP), based on the recently solved crystal structures of RNAP of Mycobacterium tuberculosis, containing a synthetic nucleic acid scaffold and rifampin. The resistance mutations were observed to alter the hydrogen-bonding and hydrophobic interactions of rifampin and the 5' ribonucleotide of the growing RNA transcript. This study demonstrates that rifampin-resistant strains of M. leprae among leprosy patients in southern India are likely to arise from mutations that affect the drug-binding site and stability of RNAP.

Indexed as

AdolescentAdultBacterial ProteinsDNA, BacterialDNA-Directed RNA PolymerasesDrug Resistance, BacterialFemaleHumansIndiaLeprostatic AgentsLeprosyMaleMicrobial Sensitivity TestsMiddle AgedMutationMycobacterium lepraeBacterial ProteinsDNA, BacterialDNA-Directed RNA PolymerasesLeprostatic AgentsRifampin

Identifiers

PMID29567948
PMCPMC5864748
OpenAlexW2802419236

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.