Evidence map›Paper›PMID 35264714›Full record

ArticleCommunications biology2022

Pleiotropic actions of phenothiazine drugs are detrimental to Gram-negative bacterial persister cells.

Sayed Golam Mohiuddin, Thao Vy Nguyen, Mehmet A Orman

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.0field-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

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Glycerol-Driven Energy and Proteostasis Underpin Antibiotic Tolerance inbioRxiv : the preprint server for biology · 2026
    Article
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  5. Review
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  9. UNRAVELING CRP/cAMP-MEDIATED METABOLIC REGULATION INbioRxiv : the preprint server for biology · 2025
    Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
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  16. 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

3 authors at 1 institution in 1 country.

Sayed Golam MohiuddinDepartment of Chemical and Biomolecular Engineering, University of Houston, Houston, TX, USA.
Thao Vy NguyenDepartment of Chemical and Biomolecular Engineering, University of Houston, Houston, TX, USA.
Mehmet A OrmanDepartment of Chemical and Biomolecular Engineering, University of Houston, Houston, TX, USA. morman@central.uh.edu.ORCID 0000-0001-8499-9154
University of Houston · US

Funding

Characterizing a Self-Digesting-Mediated Reversible Drug Tolerance Mechanism in BacteriaR01AI143643 · NIAID · UNIVERSITY OF HOUSTON · PI ORMAN, MEHMET A. · 2020 to 2024
$1.9M
Investigating "viable but non-culturable" Cell and Persister Formation MechanismsK22AI125468 · NIAID · UNIVERSITY OF HOUSTON · PI ORMAN, MEHMET A. · 2018 to 2019
$270k
NIAID NIH HHS K22 AI125468NIAID NIH HHS R01 AI143643
6 · The paper itself

Abstract

Bacterial persister cells are temporarily tolerant to bactericidal antibiotics but are not necessarily dormant and may exhibit physiological activities leading to cell damage. Based on the link between fluoroquinolone-mediated SOS responses and persister cell recovery, we screened chemicals that target fluoroquinolone persisters. Metabolic inhibitors (e.g., phenothiazines) combined with ofloxacin (OFX) perturbed persister levels in metabolically active cell populations. When metabolically stimulated, intrinsically tolerant stationary phase cells also became OFX-sensitive in the presence of phenothiazines. The effects of phenothiazines on cell metabolism and physiology are highly pleiotropic: at sublethal concentrations, phenothiazines reduce cellular metabolic, transcriptional, and translational activities; impair cell repair and recovery mechanisms; transiently perturb membrane integrity; and disrupt proton motive force by dissipating the proton concentration gradient across the cell membrane. Screening a subset of mutant strains lacking membrane-bound proteins revealed the pleiotropic effects of phenothiazines potentially rely on their ability to inhibit a wide range of critical metabolic proteins. Altogether, our study further highlights the complex roles of metabolism in persister cell formation, survival and recovery, and suggests metabolic inhibitors such as phenothiazines can be selectively detrimental to persister cells.

Indexed as

Anti-Bacterial AgentsEscherichia coliFluoroquinolonesGram-Negative BacteriaPhenothiazinesAnti-Bacterial AgentsFluoroquinolonesPhenothiazines

Identifiers

PMID35264714
PMCPMC8907348
OpenAlexW4220968640

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.