Evidence map›Paper›PMID 29461800›Full record

ArticleACS infectious diseases2018

Antisense Inhibitors Retain Activity in Pulmonary Models of Burkholderia Infection.

Seth M Daly, Carolyn R Sturge, Kimberly R Marshall-Batty, Christina F Felder-Scott, Raksha Jain, Bruce L Geller, David E Greenberg

Open access · greenAbstract read
In one paragraph

Article in ACS infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

10 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
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  7. Evaluation of accessible regions ofIranian journal of microbiology · 2021
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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

7 authors at 2 institutions in 1 country.

Seth M DalyDepartment of Internal Medicine , UT Southwestern , 5323 Harry Hines Blvd , Dallas , Texas 75390 , United States.
Carolyn R SturgeDepartment of Internal Medicine , UT Southwestern , 5323 Harry Hines Blvd , Dallas , Texas 75390 , United States.ORCID 0000-0002-6596-3356
Kimberly R Marshall-BattyDepartment of Internal Medicine , UT Southwestern , 5323 Harry Hines Blvd , Dallas , Texas 75390 , United States.
Christina F Felder-ScottDepartment of Internal Medicine , UT Southwestern , 5323 Harry Hines Blvd , Dallas , Texas 75390 , United States.
Raksha JainDepartment of Internal Medicine , UT Southwestern , 5323 Harry Hines Blvd , Dallas , Texas 75390 , United States.
Bruce L GellerDepartment of Microbiology , Oregon State University , 226 Nash Hall , Corvallis , Oregon 97331 , United States.
David E GreenbergDepartment of Internal Medicine , UT Southwestern , 5323 Harry Hines Blvd , Dallas , Texas 75390 , United States.
Southwestern Medical Center · USOregon State University · US

Funding

MOLECULAR MICROBIOLOGY TRAINING GRANTT32AI007520 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI Julie K Pfeiffer · 1997 to 2026
$7.0M
Circumventing Antibiotic Resistance with Novel Gene-Silencing TherapeuticsR33AI111753 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GELLER, BRUCE L, GREENBERG, DAVID ELIHU · 2016 to 2018
$1.4M
Gene silencing therapeutics for chronic infections in cystic fibrosisR33AI105980 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GREENBERG, DAVID ELIHU · 2015 to 2017
$1.1M
Gene silencing therapeutics for chronic infections in cystic fibrosisR21AI105980 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GREENBERG, DAVID ELIHU · 2013 to 2014
$416k
Circumventing Antibiotic Resistance with Novel Gene-Silencing TherapeuticsR21AI111753 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI GELLER, BRUCE L, GREENBERG, DAVID ELIHU · 2014 to 2015
$415k
NIAID NIH HHS R21 AI105980NIAID NIH HHS R21 AI111753NIAID NIH HHS R33 AI105980NIAID NIH HHS R33 AI111753NIAID NIH HHS T32 AI007520
6 · The paper itself

Abstract

The Burkholderia cepacia complex is a group of Gram-negative bacteria that are opportunistic pathogens in immunocompromised individuals, such as those with cystic fibrosis (CF) or chronic granulomatous disease (CGD). Burkholderia are intrinsically resistant to many antibiotics and the lack of antibiotic development necessitates novel therapeutics. Peptide-conjugated phosphorodiamidate morpholino oligomers are antisense molecules that inhibit bacterial mRNA translation. Targeting of PPMOs to the gene acpP, which is essential for membrane synthesis, lead to defects in the membrane and ultimately bactericidal activity. Exploration of additional PPMO sequences identified the ATG and Shine-Dalgarno sites as the most efficacious for targeting acpP. The CF lung is a complex microenvironment, but PPMO inhibition was still efficacious in an artificial model of CF sputum. PPMOs had low toxicity in human CF cells at doses that were antibacterial. PPMOs also reduced the bacterial burden in the lungs of immunocompromised CyBB mice, a model of CGD. Finally, the use of multiple PPMOs was efficacious in inhibiting the growth of both Burkholderia and Pseudomonas in an in vitro model of coinfection. Due to the intrinsic resistance of Burkholderia to traditional antibiotics, PPMOs represent a novel and viable approach to the treatment of Burkholderia infections.

Indexed as

AnimalsAnti-Bacterial AgentsBurkholderiaBurkholderia cepacia complexBurkholderia InfectionsCystic FibrosisDisease Models, AnimalMiceMicrobial Sensitivity TestsMorpholinosOligonucleotides, AntisensePneumonia, BacterialAnti-Bacterial AgentsMorpholinosOligonucleotides, Antisenseantisenseartificial sputumBurkholaderia cepacia complex (Bcc)peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO)pneumonia

Identifiers

PMID29461800
PMCPMC6669075
OpenAlexW2787884498

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.