ArticleThe Journal of antimicrobial chemotherapy2018
Morpholino oligomers tested in vitro, in biofilm and in vivo against multidrug-resistant Klebsiella pneumoniae.
Article in The Journal of antimicrobial chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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.
Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Developing antisense oligomer biotics "asobiotics" as precision antibacterials: designs, strategies, and considerations for future success.FEMS microbiology reviews · 2026Review
- Antimicrobial Resistance: The Answers.British journal of biomedical science · 2026Review
- Exploring the Therapeutic Potential: Antisense RNA Delivery Via Bacteriophage Platform.Iranian journal of biotechnology · 2025Review
- ASOBIOTICS 2024: an interdisciplinary symposium on antisense-based programmable RNA antibiotics.RNA (New York, N.Y.) · 2025Article
- Resilience Against Resistance: Exploring Cutting-edge Therapies for Methicillin-resistantCurrent medicinal chemistry · 2025Review
- Antisense phosphorodiamidate morpholino oligomers retain activity inFrontiers in microbiology · 2025Article
- Chemical strategies for antisense antibiotics.Chemical Society reviews · 2024Review
- Identifying Cell-Penetrating Peptides for Effectively Delivering Antimicrobial Molecules intoAntibiotics (Basel, Switzerland) · 2024Article
- A comparative analysis of peptide-delivered antisense antibiotics using diverse nucleotide mimics.RNA (New York, N.Y.) · 2024Article
- Alternative therapeutic strategies to treat antibiotic-resistant pathogens.Nature reviews. Microbiology · 2024Review
- Animal models ofFrontiers in microbiology · 2024Review
- Strategies to combat Gram-negative bacterial resistance to conventional antibacterial drugs: a review.Osong public health and research perspectives · 2023Article
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- Developing New Tools to Fight Human Pathogens: A Journey through the Advances in RNA Technologies.Microorganisms · 2022Review
- Targeting of Regulators as a Promising Approach in the Search for Novel Antimicrobial Agents.Microorganisms · 2022Article
- Innovative developments and emerging technologies in RNA therapeutics.RNA biology · 2022Article
- Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents.Frontiers in microbiology · 2022Review
- FromMicroorganisms · 2021Review
- Global RNA profiles show target selectivity and physiological effects of peptide-delivered antisense antibiotics.Nucleic acids research · 2021Article
- Delivery of oligonucleotide-based therapeutics: challenges and opportunities.EMBO molecular medicine · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Background: Klebsiella pneumoniae is an opportunistic pathogen and many strains are multidrug resistant. KPC is one of the most problematic resistance mechanisms, as it confers resistance to most β-lactams, including carbapenems. A promising platform technology for treating infections caused by MDR pathogens is the nucleic acid-like synthetic oligomers that silence bacterial gene expression by an antisense mechanism. Objectives: To test a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) in a mouse model of K. pneumoniae infection. Methods: PPMOs were designed to target various essential genes of K. pneumoniae and screened in vitro against a panel of diverse strains. The most potent PPMOs were further tested for their bactericidal effects in broth cultures and in established biofilms. Finally, a PPMO was used to treat mice infected with a KPC-expressing strain. Results: The most potent PPMOs targeted acpP, rpmB and ftsZ and had MIC75s of 0.5, 4 and 4 μM, respectively. AcpP PPMOs were bactericidal at 1-2 × MIC and reduced viable cells and biofilm mass in established biofilms. In a mouse pneumonia model, therapeutic intranasal treatment with ∼30 mg/kg AcpP PPMO improved survival by 89% and reduced bacterial burden in the lung by ∼3 logs. Survival was proportional to the dose of AcpP PPMO. Delaying treatment by 2, 8 or 24 h post-infection improved survival compared with control groups treated with PBS or scrambled sequence (Scr) PPMOs. Conclusions: PPMOs have the potential to be effective therapeutic agents against KPC-expressing, MDR K. pneumoniae.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.