Evidence map›Paper›PMID 26433781›Full record

ArticleThe Journal of antimicrobial chemotherapy2016

Rhesus θ-defensin-1 (RTD-1) exhibits in vitro and in vivo activity against cystic fibrosis strains of Pseudomonas aeruginosa.

Paul M Beringer, Timothy J Bensman, Henry Ho, Melissa Agnello, Nicole Denovel, Albert Nguyen, Annie Wong-Beringer, Rosemary She, Dat Q Tran, Samuel M Moskowitz and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

20 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. A Fun-Guide to Innate Immune Responses to Fungal Infections.Journal of fungi (Basel, Switzerland) · 2022
    Review
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  9. Host Defense Peptides as Templates for Antifungal Drug Development.Journal of fungi (Basel, Switzerland) · 2020
    Review
  10. Considerations and Caveats in Combating ESKAPE Pathogens against Nosocomial Infections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. The Role of Defensins in HIV Pathogenesis.Mediators of inflammation · 2017
    Review
  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

11 authors at 3 institutions in 1 country.

Paul M BeringerSchool of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA beringer@usc.edu.
Timothy J BensmanSchool of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Henry HoSchool of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Melissa AgnelloSchool of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Nicole DenovelSchool of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Albert NguyenSchool of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Annie Wong-BeringerSchool of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Rosemary SheDepartment of Pathology & Laboratory Medicine, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Dat Q TranDepartment of Pathology & Laboratory Medicine, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Samuel M MoskowitzDepartment of Pediatrics, Massachusetts General Hospital and Harvard Medical School, 275 Cambridge Street, Boston, MA, USA.
Michael E SelstedDepartment of Pathology & Laboratory Medicine, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA USC Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA, USA.
University of Southern California · USHarvard University · USUSC Norris Comprehensive Cancer Center · US

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Fumito Ito · 1985 to 2026
$181.4M
DOCTORAL AND POST-DOCTORAL TRAINING IN CRANIOFACIAL BIOLOGYT90DE021982 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI PAINE, MICHAEL LANSDELL · 2011 to 2025
$6.2M
Regulation of Mucosal Immunity by Pro- and Anti-inflammatory Salivary DefensinsR01DE021341 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SELSTED, MICHAEL E · 2010 to 2014
$1.9M
MOLECULAR ASPECTS OF LEUKOCYTE ANTIMICROBIAL PEPTIDESR01AI022931 · NIAID · UNIVERSITY OF SOUTHERN CALIFORNIA · PI SELSTED, MICHAEL E · 1986 to 2016
$1.7M
NCI NIH HHS P30 CA014089NCI NIH HHS P30CA014089NIAID NIH HHS R01 AI022931NIAID NIH HHS R01AI22931NIDCR NIH HHS 5T90DE021982NIDCR NIH HHS R01 DE021341NIDCR NIH HHS R01DE 021341
6 · The paper itself

Abstract

objectivesChronic endobronchial infections with Pseudomonas aeruginosa contribute to bronchiectasis and progressive loss of lung function in patients with cystic fibrosis. This study aimed to evaluate the therapeutic potential of a novel macrocyclic peptide, rhesus θ-defensin-1 (RTD-1), by characterizing its in vitro antipseudomonal activity and in vivo efficacy in a murine model of chronic Pseudomonas lung infection.

methodsAntibacterial testing of RTD-1 was performed on 41 clinical isolates of P. aeruginosa obtained from cystic fibrosis patients. MIC, MBC, time-kill and post-antibiotic effects were evaluated following CLSI-recommended methodology, but using anion-depleted Mueller-Hinton broth. RTD-1 was nebulized daily for 7 days to cystic fibrosis transmembrane conductance regulator (CFTR) F508del-homozygous mice infected using the agar bead model of chronic P. aeruginosa lung infection. In vivo activity was evaluated by change in lung bacterial burden, airway leucocytes and body weight.

resultsRTD-1 exhibited potent in vitro bactericidal activity against mucoid and non-mucoid strains of P. aeruginosa (MIC90 = 8 mg/L). Cross-resistance was not observed when tested against MDR and colistin-resistant isolates. Time-kill studies indicated very rapid, concentration-dependent bactericidal activity of RTD-1 with ≥3 log10 cfu/mL reductions at concentrations ≥4× MIC. No post-antibiotic effect was observed. In vivo, nebulized treatment with RTD-1 significantly decreased lung P. aeruginosa burden (mean difference of -1.30 log10 cfu; P = 0.0061), airway leucocytes (mean difference of -0.37 log10; P = 0.0012) and weight loss (mean difference of -12.62% at day 7; P < 0.05) when compared with controls.

conclusionsThis study suggests that RTD-1 is a promising potential therapeutic agent for cystic fibrosis airway disease.

Indexed as

Macaca mulattaAnimalsAnti-Bacterial AgentsBacterial LoadBody WeightCystic FibrosisDefensinsDisease Models, AnimalHumansLeukocyte CountLungMaleMice, Inbred C57BLMicrobial Sensitivity TestsMicrobial ViabilityPseudomonas aeruginosaAnti-Bacterial AgentsDefensinstheta-defensin

Identifiers

PMID26433781
PMCPMC5007590
OpenAlexW2234043297

What OpenQuestion holds

Textmetadata
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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.