Evidence map›Paper›PMID 24558351›Full record

ArticlePLoS biology2014

Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.

Patrick Kaiser, Roland R Regoes, Tamas Dolowschiak, Sandra Y Wotzka, Jette Lengefeld, Emma Slack, Andrew J Grant, Martin Ackermann, Wolf-Dietrich Hardt

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
7.0field-weighted citation impact, top 2% 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

81 citing papers in PubMed, 148 citations in OpenAlex.

  1. Review
  2. Microorganisms · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Quantification ofeLife · 2025
    Article
  9. Review
  10. Article
  11. Quantification ofbioRxiv : the preprint server for biology · 2024
    Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Microbiology spectrum · 2023
    Article
  20. Article

21 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Patrick KaiserInstitute of Microbiology, Eidgenössische Technische Hochschule ETH, Zurich, Switzerland.
Roland R RegoesInstitute of Integrative Biology, Eidgenössische Technische Hochschule ETH, Zurich, Switzerland.
Tamas DolowschiakInstitute of Microbiology, Eidgenössische Technische Hochschule ETH, Zurich, Switzerland.
Sandra Y WotzkaInstitute of Microbiology, Eidgenössische Technische Hochschule ETH, Zurich, Switzerland.
Jette LengefeldInstitute of Microbiology, Eidgenössische Technische Hochschule ETH, Zurich, Switzerland.
Emma SlackInstitute of Microbiology, Eidgenössische Technische Hochschule ETH, Zurich, Switzerland.
Andrew J GrantDepartment of Veterinary Medicine and Cambridge Infectious Diseases Consortium, University of Cambridge, Cambridge, United Kingdom.
Martin AckermannDepartment of Environmental Systems Science, ETH Zurich, and Department of Environmental Microbiology, Eawag, Switzerland.
Wolf-Dietrich HardtInstitute of Microbiology, Eidgenössische Technische Hochschule ETH, Zurich, Switzerland.
ETH Zurich · CHBoard of the Swiss Federal Institutes of Technology · CHUniversity of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.

Indexed as

AnimalsAnti-Bacterial AgentsBacterial LoadCecumCiprofloxacinDendritic CellsDiarrheaDrug Resistance, BacterialLipopolysaccharidesLymph NodesMiceMice, Inbred C57BLMicrobial Sensitivity TestsPhenotypeSalmonella InfectionsSalmonella typhimuriumAnti-Bacterial AgentsCiprofloxacinLipopolysaccharides

Identifiers

PMID24558351
PMCPMC3928039
OpenAlexW1973852640

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.