Evidence map›Paper›PMID 30742339›Full record

ArticleMolecular microbiology2019

Increased drug permeability of a stiffened mycobacterial outer membrane in cells lacking MFS transporter Rv1410 and lipoprotein LprG.

Michael Hohl, Sille Remm, Haig A Eskandarian, Michael Dal Molin, Fabian M Arnold, Lea M Hürlimann, Andri Krügel, Georg E Fantner, Peter Sander, Markus A Seeger

Open access · hybridAbstract read
In one paragraph

Article in Molecular microbiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.2field-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

18 citing papers in PubMed, 32 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Biomolecules · 2022
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. 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

10 authors at 3 institutions in 1 country.

Michael HohlInstitute of Medical Microbiology, University of Zurich, Zürich, Switzerland.ORCID 0000-0002-6046-4865
Sille RemmInstitute of Medical Microbiology, University of Zurich, Zürich, Switzerland.ORCID 0000-0001-5204-4556
Haig A EskandarianGlobal Health Institute, École polytechnique fédérale de Lausanne, EPFL, Lausanne, Switzerland.ORCID 0000-0002-0610-0550
Michael Dal MolinInstitute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
Fabian M ArnoldInstitute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
Lea M HürlimannInstitute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
Andri KrügelInstitute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
Georg E FantnerInterfaculty Institute for Bioengineering, École polytechnique fédérale de Lausanne, EPFL, Lausanne, Switzerland.ORCID 0000-0001-5889-3022
Peter SanderInstitute of Medical Microbiology, University of Zurich, Zürich, Switzerland.
Markus A SeegerInstitute of Medical Microbiology, University of Zurich, Zürich, Switzerland.ORCID 0000-0003-1761-8571
University of Zurich · CHBioengineering (Switzerland) · CHÉcole Polytechnique Fédérale de Lausanne · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The major facilitator superfamily transporter Rv1410 and the lipoprotein LprG (Rv1411) are encoded by a conserved two-gene operon and contribute to virulence in Mycobacterium tuberculosis. Rv1410 was originally postulated to function as a drug efflux pump, but recent studies suggested that Rv1410 and LprG work in concert to insert triacylglycerides and lipoarabinomannans into the outer membrane. Here, we conducted microscopic analyses of Mycobacterium smegmatis lacking the operon and observed a cell separation defect, while surface rigidity measured by atomic force microscopy was found to be increased. Whereas Rv1410 expressed in Lactococcus lactis did not confer drug resistance, deletion of the operon in Mycobacterium abscessus and M. smegmatis resulted in increased susceptibility toward vancomycin, novobiocin and rifampicin. A homology model of Rv1410 revealed a periplasmic loop as well as a highly conserved aspartate, which were found to be essential for the operon's function. Interestingly, influx of the fluorescent dyes BCECF-AM and calcein-AM in de-energized M. smegmatis cells was faster in the deletion mutant. Our results unambiguously show that elevated drug susceptibility in the deletion mutant is caused by increased drug influx through a defective mycobacterial cell envelope and not by drug efflux mediated by Rv1410.

Indexed as

OperonAnti-Bacterial AgentsBacterial ProteinsCell MembraneGene DeletionLactococcus lactisLipopolysaccharidesMembrane Transport ProteinsMicroscopy, Atomic ForceMicroscopy, Electron, TransmissionMutationMycobacterium abscessusMycobacterium smegmatisMycobacterium tuberculosisPermeabilityProtein Structure, TertiaryAnti-Bacterial AgentsBacterial ProteinslipoarabinomannanLipopolysaccharidesMembrane Transport ProteinsP55 protein, MycobacteriumRifampin

Identifiers

PMID30742339
PMCPMC6519032
OpenAlexW2914455821

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.