Evidence map›Paper›PMID 27986898›Full record

ArticleThe Journal of antimicrobial chemotherapy2017

Antimicrobial activity of antisense peptide-peptide nucleic acid conjugates against non-typeable Haemophilus influenzae in planktonic and biofilm forms.

Taketo Otsuka, Aimee L Brauer, Charmaine Kirkham, Erin K Sully, Melinda M Pettigrew, Yong Kong, Bruce L Geller, Timothy F Murphy

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 2 pooled it
2.0field-weighted citation impact, top 14% 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

19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.

  1. Pooled it
  2. Understanding bacterial biofilms: From definition to treatment strategies.Frontiers in cellular and infection microbiology · 2023
    Pooled it
  3. Article
  4. Review
  5. Article
  6. Article
  7. Selected strategies to fight pathogenic bacteria.Journal of enzyme inhibition and medicinal chemistry · 2023
    Review
  8. Review
  9. Review
  10. Review
  11. Specific and Global RNA Regulators inInternational journal of molecular sciences · 2021
    Review
  12. Novel Strategies to Combat Bacterial Biofilms.Molecular biotechnology · 2021
    Review
  13. Article
  14. Transcriptome-based design of antisense inhibitors potentiates carbapenem efficacy in CREProceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  15. Biofilm architecture: An emerging synthetic biology target.Synthetic and systems biotechnology · 2020
    Review
  16. Review
  17. Article
  18. Article
  19. Advances in therapeutic bacterial antisense biotechnology.Applied microbiology and biotechnology · 2018
    Review
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 3 institutions in 1 country.

Taketo OtsukaDivision of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA.
Aimee L BrauerDivision of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA.
Charmaine KirkhamDivision of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA.
Erin K SullyDepartment of Microbiology, Oregon State University, Corvallis, OR, USA.
Melinda M PettigrewDepartment of Epidemiology of Microbial Diseases, Yale School of Public Health, Yale University, New Haven, CT, USA.
Yong KongDepartment of Molecular Biophysics and Biochemistry, W.M. Keck Foundation Biotechnology Resource Laboratory, Yale University, New Haven, CT, USA.
Bruce L GellerDepartment of Microbiology, Oregon State University, Corvallis, OR, USA.
Timothy F MurphyDivision of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA murphyt@buffalo.edu.
University at Buffalo, State University of New York · USOregon State University · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
University of Buffalo Clinical and Translational Science Institute - Supplement SchulyerUL1TR001412 · NCATS · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2015 to 2024
$33.8M
Persistent H. influenzae in COPD - virulence, vaccines and antibiotic resistanceR01AI019641 · NIAID · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 1985 to 2023
$7.9M
Selective eradication of nasopharyngeal colonization to prevent otitis mediaR21DC012917 · NIDCD · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI MURPHY, TIMOTHY F · 2014 to 2015
$446k
NCATS NIH HHS UL1 TR001412NCATS NIH HHS UL1 TR001863NIAID NIH HHS R01 AI019641NIDCD NIH HHS R21 DC012917
6 · The paper itself

Abstract

backgroundAntisense peptide nucleic acids (PNAs) are synthetic polymers that mimic DNA/RNA and inhibit bacterial gene expression in a sequence-specific manner.

methodsTo assess activity against non-typeable Haemophilus influenzae (NTHi), we designed six PNA-peptides that target acpP, encoding an acyl carrier protein. MICs and minimum biofilm eradication concentrations (MBECs) were determined. Resistant strains were selected by serial passages on media with a sub-MIC concentration of acpP-PNA.

resultsThe MICs of six acpP-PNA-peptides were 2.9-11 mg/L (0.63-2.5 μmol/L) for 20 clinical isolates, indicating susceptibility of planktonic NTHi. By contrast, MBECs were up to 179 mg/L (40 μmol/L). Compared with one original PNA-peptide (acpP-PNA1-3'N), an optimized PNA-peptide (acpP-PNA14-5'L) differs in PNA sequence and has a 5' membrane-penetrating peptide with a linker between the PNA and peptide. The optimized PNA-peptide had an MBEC ranging from 11 to 23 mg/L (2.5-5 μmol/L), indicating susceptibility. A resistant strain that was selected by the original acpP-PNA1-3'N had an SNP that introduced a stop codon in NTHI0044, which is predicted to encode an ATP-binding protein of a conserved ABC transporter. Deletion of NTHI0044 caused resistance to the original acpP-PNA1-3'N, but showed no effect on susceptibility to the optimized acpP-PNA14-5'L. The WT strain remained susceptible to the optimized PNA-peptide after 30 serial passages on media containing the optimized PNA-peptide.

conclusionsA PNA-peptide that targets acpP, has a 5' membrane-penetrating peptide and has a linker shows excellent activity against planktonic and biofilm NTHi and is associated with a low risk for induction of resistance.

Indexed as

Acyl Carrier ProteinAnti-Bacterial AgentsBacterial ProteinsBiofilmsDrug Resistance, BacterialHaemophilus influenzaeMicrobial Sensitivity TestsOligodeoxyribonucleotides, AntisensePeptide Nucleic AcidsSerial PassageAcyl Carrier ProteinAnti-Bacterial AgentsBacterial ProteinsOligodeoxyribonucleotides, AntisensePeptide Nucleic Acids

Identifiers

PMID27986898
PMCPMC5161047
OpenAlexW2526916198

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.