Evidence map›Paper›PMID 30556355›Full record

ArticleMolecular microbiology2019

Inhibition of Pseudomonas aeruginosa and Mycobacterium tuberculosis disulfide bond forming enzymes.

Cristina Landeta, Laura McPartland, Ngoc Q Tran, Brian M Meehan, Yifan Zhang, Zaidi Tanweer, Shoko Wakabayashi, Jeremy Rock, Taehyun Kim, Deepak Balasubramanian and 8 more

Open access · bronzeAbstract 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 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
0.7field-weighted citation impact, top 37% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

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  8. Distinct enzymatic strategies forCritical reviews in biochemistry and molecular biology · 2023
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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

18 authors at 2 institutions in 1 country.

Cristina LandetaDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4065-9646
Laura McPartlandDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Ngoc Q TranDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Brian M MeehanDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Yifan ZhangDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Zaidi TanweerDivision of Infectious Diseases. Department of Medicine. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Shoko WakabayashiDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Jeremy RockDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Taehyun KimDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Deepak BalasubramanianDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Rebecca AudetteDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Melody TooskyDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Jessica PinkhamDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Eric J RubinDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Stephen LoryDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-4079-5229
Gerald PierDivision of Infectious Diseases. Department of Medicine. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Dana BoydDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Jon BeckwithDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Harvard University · USBrigham and Women's Hospital · US

Funding

Microbial Diversity in Mechanisms of Disulfide Bond Formation and ReductionR01GM041883 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI BOYD, DANA · 1989 to 2014
$7.8M
NIGMS NIH HHS R01 GM041883
6 · The paper itself

Abstract

In bacteria, disulfide bonds confer stability on many proteins exported to the cell envelope or beyond, including bacterial virulence factors. Thus, proteins involved in disulfide bond formation represent good targets for the development of inhibitors that can act as antibiotics or anti-virulence agents, resulting in the simultaneous inactivation of several types of virulence factors. Here, we present evidence that the disulfide bond forming enzymes, DsbB and VKOR, are required for Pseudomonas aeruginosa pathogenicity and Mycobacterium tuberculosis survival respectively. We also report the results of a HTS of 216,767 compounds tested against P. aeruginosa DsbB1 and M. tuberculosis VKOR using Escherichia coli cells. Since both P. aeruginosa DsbB1 and M. tuberculosis VKOR complement an E. coli dsbB knockout, we screened simultaneously for inhibitors of each complemented E. coli strain expressing a disulfide-bond sensitive β-galactosidase reported previously. The properties of several inhibitors obtained from these screens suggest they are a starting point for chemical modifications with potential for future antibacterial development.

Indexed as

AnimalsBacterial ProteinsDisulfidesEscherichia coliFemaleHigh-Throughput Screening AssaysMembrane ProteinsMiceMice, Inbred C57BLMycobacterium tuberculosisPseudomonas aeruginosaSmall Molecule LibrariesVirulenceVirulence FactorsBacterial ProteinsDisulfidesDsbB protein, BacteriaMembrane ProteinsSmall Molecule LibrariesVirulence Factors

Identifiers

PMID30556355
PMCPMC6458069
OpenAlexW2904103758

What OpenQuestion holds

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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.