Evidence map›Paper›PMID 23002228›Full record

ArticleJournal of bacteriology2012

Upregulation of the phthiocerol dimycocerosate biosynthetic pathway by rifampin-resistant, rpoB mutant Mycobacterium tuberculosis.

Gregory P Bisson, Carolina Mehaffy, Corey Broeckling, Jessica Prenni, Dalin Rifat, Desmond S Lun, Marcos Burgos, Drew Weissman, Petros C Karakousis, Karen Dobos

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Journal of bacteriology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

59 citing papers in PubMed, 102 citations in OpenAlex.

  1. Review
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  14. Drug-resistant strains ofFrontiers in cellular and infection microbiology · 2023
    Review
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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

10 authors at 6 institutions in 2 countries.

Gregory P BissonDivision of Infectious Diseases, Department of Medicine, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Carolina Mehaffy
Corey Broeckling
Jessica Prenni
Dalin Rifat
Desmond S Lun
Marcos Burgos
Drew Weissman
Petros C Karakousis
Karen Dobos
Colorado State University · USUniversity of Pennsylvania · USJohns Hopkins Medicine · USJohns Hopkins University · USRutgers, The State University of New Jersey · USUniversity of New Mexico · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multidrug-resistant tuberculosis has emerged as a major threat to tuberculosis control. Phylogenetically related rifampin-resistant actinomycetes with mutations mapping to clinically dominant Mycobacterium tuberculosis mutations in the rpoB gene show upregulation of gene networks encoding secondary metabolites. We compared the expressed proteomes and metabolomes of two fully drug-susceptible clinical strains of M. tuberculosis (wild type) to those of their respective rifampin-resistant, rpoB mutant progeny strains with confirmed rifampin monoresistance following antitubercular therapy. Each of these strains was also used to infect gamma interferon- and lipopolysaccharide-activated murine J774A.1 macrophages to analyze transcriptional responses in a physiologically relevant model. Both rpoB mutants showed significant upregulation of the polyketide synthase genes ppsA-ppsE and drrA, which constitute an operon encoding multifunctional enzymes involved in the biosynthesis of phthiocerol dimycocerosate and other lipids in M. tuberculosis, but also of various secondary metabolites in related organisms, including antibiotics, such as erythromycin and rifamycins. ppsA (Rv2931), ppsB (Rv2932), and ppsC (Rv2933) were also found to be upregulated more than 10-fold in the Beijing rpoB mutant strain relative to its wild-type parent strain during infection of activated murine macrophages. In addition, metabolomics identified precursors of phthiocerol dimycocerosate, but not the intact molecule itself, in greater abundance in both rpoB mutant isolates. These data suggest that rpoB mutation in M. tuberculosis may trigger compensatory transcriptional changes in secondary metabolism genes analogous to those observed in related actinobacteria. These findings may assist in developing novel methods to diagnose and treat drug-resistant M. tuberculosis infections.

Indexed as

Drug Resistance, BacterialGene Expression Regulation, BacterialAnimalsAntitubercular AgentsBacterial ProteinsBiosynthetic PathwaysCell LineDNA-Directed RNA PolymerasesGene Expression ProfilingHumansLipidsMacrophagesMetabolomeMiceMicrobial Sensitivity TestsMutant ProteinsAntitubercular AgentsBacterial ProteinsDNA-Directed RNA PolymerasesLipidsMutant Proteinsphthiocerol dimycocerosateProteomeRifampinrpoB protein, Mycobacterium tuberculosis

Identifiers

PMID23002228
PMCPMC3497527
OpenAlexW1972283322

What OpenQuestion holds

Textmetadata
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.