Evidence map›Paper›PMID 20438352›Full record

ArticleThe Journal of infectious diseases2010

Antisense phosphorodiamidate morpholino oligomers targeted to an essential gene inhibit Burkholderia cepacia complex.

David E Greenberg, Kimberly R Marshall-Batty, Lauren R Brinster, Kol A Zarember, Pamela A Shaw, Brett L Mellbye, Patrick L Iversen, Steven M Holland, Bruce L Geller

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of infectious diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
5.5field-weighted citation impact, top 4% 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

50 citing papers in PubMed, 81 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Chemical strategies for antisense antibiotics.Chemical Society reviews · 2024
    Review
  5. Review
  6. Review
  7. Sequence specificity defines the effectiveness of PPMOs targetingAntimicrobial agents and chemotherapy · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Targeting of the EssentialBiomedicines · 2021
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Advances in therapeutic bacterial antisense biotechnology.Applied microbiology and biotechnology · 2018
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

David E GreenbergImmunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, Office of Research Services, National Institutes of Health, Bethesda, Maryland, USA. degreenberg@niaid.nih.gov
Kimberly R Marshall-Batty
Lauren R Brinster
Kol A Zarember
Pamela A Shaw
Brett L Mellbye
Patrick L Iversen
Steven M Holland
Bruce L Geller
National Institutes of Health · USOregon State University · USOffice of Research Services · US

Funding

Transgenic Animal Models Of Human Immune DefectsZIAAI000646 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI HOLLAND, STEVEN · 2009 to 2025
$22.2M
Intramural NIH HHS Z99 AI999999
6 · The paper itself

Abstract

backgroundMembers of the Burkholderia cepacia complex (Bcc) cause considerable morbidity and mortality in patients with chronic granulomatous disease and cystic fibrosis. Many Bcc strains are antibiotic resistant, which requires the exploration of novel antimicrobial approaches, including antisense technologies such as phosphorodiamidate morpholino oligomers (PMOs).

methodsPeptide-conjugated PMOs (PPMOs) were developed to target acpP, which encodes an acyl carrier protein (AcpP) that is thought to be essential for growth. Their antimicrobial activities were tested against different strains of Bcc in vitro and in infection models.

resultsPPMOs targeting acpP were bactericidal against clinical isolates of Bcc (>4 log reduction), whereas a PPMO with a scrambled base sequence (scrambled PPMO) had no effect on growth. Human neutrophils were infected with Burkholderia multivorans and treated with AcpP PPMO. AcpP PPMO augmented killing, compared with neutrophils alone and compared with neutrophils alone plus scrambled PPMO. Mice with chronic granulomatous disease that were infected with B. multivorans were treated with AcpP PPMO, scrambled PPMO, or water at 0, 3, and 6 h after infection. Compared with water-treated control mice, the AcpP PPMO-treated mice showed an approximately 80% reduction in the risk of dying by day 30 of the experiment and relatively little pathology.

conclusionAcpP PPMO is active against Bcc infections in vitro and in vivo.

Indexed as

Acyl Carrier ProteinAnimalsAnti-Bacterial AgentsBacterial ProteinsBurkholderia cepacia complexBurkholderia InfectionsCell SurvivalDisease Models, AnimalGranulomatous Disease, ChronicHumansMiceMicrobial Sensitivity TestsMicrobial ViabilityMorpholinesMorpholinosNeutrophilsAcyl Carrier ProteinAnti-Bacterial AgentsBacterial ProteinsMorpholinesMorpholinosOligodeoxyribonucleotides, Antisense

Identifiers

PMID20438352
PMCPMC2872041
OpenAlexW2152151480

What OpenQuestion holds

Textmetadata
LicenceTDM
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.