Evidence map›Paper›PMID 34097492›Full record

ArticleAntimicrobial agents and chemotherapy2021

The AcrAB-TolC Efflux Pump Impacts Persistence and Resistance Development in Stationary-Phase Escherichia coli following Delafloxacin Treatment.

Brandon A Byrd, Blesing Zenick, Maria C Rocha-Granados, Hanna E Englander, Patricia J Hare, Travis J LaGree, Angela M DeMarco, Wendy W K Mok

Open access · greenAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 16% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Molecular Basis of Persister Awakening and Lag-Phase Recovery inInternational journal of molecular sciences · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Antibiotic-recalcitrant Salmonella during infection.Nature reviews. Microbiology · 2025
    Review
  11. Deciphering meropenem persistence inAntimicrobial agents and chemotherapy · 2025
    Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
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

8 authors at 2 institutions in 1 country.

Brandon A Byrd *Department of Molecular Biology & Biophysics, UCONN Health, Farmington, Connecticut, USA.
Blesing Zenick *Department of Molecular Biology & Biophysics, UCONN Health, Farmington, Connecticut, USA.
Maria C Rocha-Granados *Department of Molecular Biology & Biophysics, UCONN Health, Farmington, Connecticut, USA.
Hanna E EnglanderDepartment of Physiology & Neurobiology, University of Connecticut, Storrs, Connecticut, USA.
Patricia J HareDepartment of Molecular Biology & Biophysics, UCONN Health, Farmington, Connecticut, USA.
Travis J LaGreeDepartment of Molecular Biology & Biophysics, UCONN Health, Farmington, Connecticut, USA.
Angela M DeMarcoDepartment of Molecular Biology & Biophysics, UCONN Health, Farmington, Connecticut, USA.
Wendy W K MokDepartment of Molecular Biology & Biophysics, UCONN Health, Farmington, Connecticut, USA.
UConn Health · USUniversity of Connecticut · US

Funding

Skeletal, Craniofacial and Oral Biology Training GrantT90DE021989 · NIDCR · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI MINA, MINA · 2011 to 2022
$4.5M
Skeletal, Craniofacial and Oral Biology Training GrantT90DE033006 · NIDCR · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI FRANK C NICHOLS · 2023 to 2026
$2.0M
NIDCR NIH HHS T90 DE021989NIDCR NIH HHS T90 DE033006
6 · The paper itself

Abstract

Bacteria have a repertoire of strategies to overcome antibiotics in clinical use, complicating our ability to treat and cure infectious diseases. In addition to evolving resistance, bacteria within genetically clonal cultures can undergo transient phenotypic changes and tolerate high doses of antibiotics. These cells, termed persisters, exhibit heterogeneous phenotypes; the strategies that a bacterial population deploys to overcome one class of antibiotics can be distinct from those needed to survive treatment with drugs with another mode of action. It was previously reported that fluoroquinolones, which target DNA topoisomerases, retain the capacity to kill nongrowing bacteria that tolerate other classes of antibiotics. Here, we show that in Escherichia coli stationary-phase cultures and colony biofilms, persisters that survive treatment with the anionic fluoroquinolone delafloxacin depend on the AcrAB-TolC efflux pump. In contrast, we did not detect this dependence on AcrAB-TolC in E. coli persisters that survive treatment with three other fluoroquinolone compounds. We found that the loss of AcrAB-TolC activity via genetic mutations or chemical inhibition not only reduces delafloxacin persistence in nongrowing E. coli MG1655 or EDL933 (an E. coli O157:H7 strain), but it limits resistance development in progenies derived from delafloxacin persisters that were given the opportunity to recover in nutritive medium following antibiotic treatment. Our findings highlight the heterogeneity in defense mechanisms that persisters use to overcome different compounds within the same class of antibiotics. They further indicate that efflux pump inhibitors can potentiate the activity of delafloxacin against stationary-phase E. coli and block resistance development in delafloxacin persister progenies.

Indexed as

Escherichia coliEscherichia coli ProteinsAnti-Bacterial AgentsCarrier ProteinsFluoroquinolonesAcrAB-TolC protein, E coliAnti-Bacterial AgentsCarrier ProteinsdelafloxacinEscherichia coli ProteinsFluoroquinolonesantibiotic persistenceantibiotic resistancebiofilmsfluoroquinoloneheterogeneity

Identifiers

PMID34097492
PMCPMC8284433
OpenAlexW3168710920

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.