دورية أكاديمية
The Designed Pore-Forming Antimicrobial Peptide C14R Combines Excellent Activity against the Major Opportunistic Human Pathogen Pseudomonas aeruginosa with Low Cytotoxicity
العنوان: | The Designed Pore-Forming Antimicrobial Peptide C14R Combines Excellent Activity against the Major Opportunistic Human Pathogen Pseudomonas aeruginosa with Low Cytotoxicity |
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المؤلفون: | Vanessa Mildenberger, Daniel Alpízar-Pedraza, Ernesto M. Martell-Huguet, Markus Krämer, Grigory Bolotnikov, Anselmo J. Otero-Gonzalez, Tanja Weil, Armando Rodriguez-Alfonso, Nico Preising, Ludger Ständker, Verena Vogel, Barbara Spellerberg, Ann-Kathrin Kissmann, Frank Rosenau |
المصدر: | Pharmaceuticals, Vol 17, Iss 1, p 83 (2024) |
بيانات النشر: | MDPI AG, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Medicine LCC:Pharmacy and materia medica |
مصطلحات موضوعية: | antimicrobial peptides, clinical isolates, pore-formation, Pseudomonas aeruginosa, Medicine, Pharmacy and materia medica, RS1-441 |
الوصف: | The diminishing portfolio of mankind’s available antibiotics urges science to develop novel potent drugs. Here, we present a peptide fitting the typical blueprint of amphipathic and membrane-active antimicrobial peptides, denominated C14R. This 2 kDa peptide consists of 16 amino acid residues, with seven being either hydrophobic, aromatic, or non-polar, and nine being polar or positively charged, strictly separated on opposite sides of the predicted α-helix. The affinity of the peptide C14R to P. aeruginosa membranes and its intrinsic tendency to productively insert into membranes of such composition were analyzed by dynamic simulations. Its biological impact on the viability of two different P. aeruginosa reference strains was demonstrated by determining the minimal inhibitory concentrations (MICs), which were found to be in the range of 10–15 µg/mL. C14R’s pore-forming capability was verified in a permeabilization assay based on the peptide-triggered uptake of fluorescent dyes into the bacterial cells. Finally, the peptide was used in radial diffusion assays, which are commonly used for susceptibility testing of antimicrobial peptides in clinical microbiology. In comparison to reference strains, six clinical P. aeruginosa isolates were clearly affected, thereby paving the way for further in-depth analyses of C14R as a promising new AMP drug in the future. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1424-8247 51596490 |
العلاقة: | https://www.mdpi.com/1424-8247/17/1/83Test; https://doaj.org/toc/1424-8247Test |
DOI: | 10.3390/ph17010083 |
الوصول الحر: | https://doaj.org/article/023e0cb51596490b8b09176303bf689eTest |
رقم الانضمام: | edsdoj.023e0cb51596490b8b09176303bf689e |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14248247 51596490 |
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DOI: | 10.3390/ph17010083 |