ArticleAntimicrobial agents and chemotherapy2012
The oligo-acyl lysyl antimicrobial peptide C₁₂K-2β₁₂ exhibits a dual mechanism of action and demonstrates strong in vivo efficacy against Helicobacter pylori.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- A Bioresponsive Genetically Encoded Antimicrobial Crystal for the Oral Treatment of Helicobacter Pylori Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Evaluation of the Efficiency of Random and Diblock Methacrylate-Based Amphiphilic Cationic Polymers against Major Bacterial Pathogens Associated with Cystic Fibrosis.Antibiotics (Basel, Switzerland) · 2023Article
- Antimicrobial Peptides and Cationic Nanoparticles: A Broad-Spectrum Weapon to Fight Multi-Drug Resistance Not Only in Bacteria.International journal of molecular sciences · 2022Review
- Mechanism of Antimicrobial Peptides: Antimicrobial, Anti-Inflammatory and Antibiofilm Activities.International journal of molecular sciences · 2021Review
- The Emergence of Multidrug-ResistantAntibiotics (Basel, Switzerland) · 2021Review
- Transformation ofPathogens (Basel, Switzerland) · 2020Review
- Unraveling the bioactivity of anticancer peptides as deduced from machine learning.EXCLI journal · 2018Review
- Selective killing ofProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs.Molecules (Basel, Switzerland) · 2017Review
- Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications.Oncotarget · 2017Review
- β-Defensins in the Fight against Helicobacter pylori.Molecules (Basel, Switzerland) · 2017Review
- Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria.Drug design, development and therapy · 2017Article
- Imaging the antimicrobial mechanism(s) of cathelicidin-2.Scientific reports · 2016Article
- Antibiotic treatment for Helicobacter pylori: Is the end coming?World journal of gastrointestinal pharmacology and therapeutics · 2015Review
- Article
- Nontraditional therapies to treat Helicobacter pylori infection.Journal of microbiology (Seoul, Korea) · 2014Review
- The antimicrobial lysine-peptoid hybrid LP5 inhibits DNA replication and induces the SOS response in Staphylococcus aureus.BMC microbiology · 2013Article
- Antibacterial activities of almond skins on cagA-positive and-negative clinical isolates of Helicobacter pylori.BMC microbiology · 2013Article
- In vitro characterization of the anti-bacterial activity of SQ109 against Helicobacter pylori.PloS one · 2013Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Helicobacter pylori has developed antimicrobial resistance to virtually all current antibiotics. Thus, there is a pressing need to develop new anti-H. pylori therapies. We recently described a novel oligo-acyl-lysyl (OAK) antimicrobial peptidomimetic, C(12)K-2β(12), that shows potent in vitro bactericidal activity against H. pylori. Herein, we define the mechanism of action and evaluate the in vivo efficacy of C(12)K-2β(12) against H. pylori after experimental infection of Mongolian gerbils. We demonstrate using a 1-N-phenylnaphthylamine (fluorescent probe) uptake assay and electron microscopy that C(12)K-2β(12) rapidly permeabilizes the bacterial membrane and creates pores that cause bacterial cell lysis. Furthermore, using nucleic acid binding assays, Western blots, and confocal microscopy, we show that C(12)K-2β(12) can cross the bacterial membranes into the cytoplasm and tightly bind to bacterial DNA, RNA, and proteins, a property that may result in inhibition of enzymatic activities and macromolecule synthesis. To define the in vivo efficacy of C(12)K-2β(12), H. pylori-infected gerbils were orogastrically treated with increasing doses and concentrations of C(12)K-2β(12) 1 day or 1 week postinfection. The efficacy of C(12)K-2β(12) was strongest in animals that received the largest number of doses at the highest concentration, indicating dose-dependent activity of the peptide (P < 0.001 by analysis of variance [ANOVA]) regardless of the timing of the treatment with C(12)K-2β(12). Overall, our results demonstrate a dual mode of action of C(12)K-2β(12) against the H. pylori membrane and cytoplasmic components. Moreover, and consistent with the previously reported in vitro efficacy, C(12)K-2β(12) shows significant in vivo efficacy against H. pylori when used as monotherapy. Therefore, OAK peptides may be a valuable resource for therapeutic treatment of H. pylori infection.
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