Antimicrobial peptides RI8 and RW8 target bacterial membranes and genomic DNA to overcome drug resistance
Abstract
The global rise of multidrug-resistant (MDR) pathogens invalidates conventional antibiotics, while natural antimicrobial peptides (AMPs) lack proteolytic stability and precise targeting. This study reports a protease-resistant symmetric (RRYY)2P(YYRR)2 scaffold (Y = isoleucine/tryptophan) with alternating cationic-hydrophobic repeats, a central proline hinge, and palindromic topology for dual bacterial membrane-genomic DNA targeting. Two derived peptides, RI8 and RW8, were characterized: RI8 showed broad-spectrum activity against MDR pathogens (MIC: 2-16 μg/mL), high therapeutic index (39.4), negligible hemolysis (<1% at 128 μg/mL), and retained efficacy in physiological salts/serum. RW8 exhibited robust protease resistance (1-2× MIC vs trypsin/chymotrypsin, 0.5× MIC vs 8 mg/mL pepsin for 8 h) and Staphylococcus aureus biofilm inhibition (71.4% at 2× MIC) via downregulating icaD/icaB/sarA. Mechanistically, both peptides disrupted bacterial membranes and bound genomic DNA; molecular dynamics simulations confirmed membrane insertion via helix-to-coil transition. In murine models, RI8/RW8 accelerated MDR-infected wound healing and reduced bacterial burdens by 2-5 logs; for S. aureus pneumonia, they outperformed levofloxacin (3-5 vs 2 logs bacterial load reduction) and restored immune function (improved thymus index, reduced pro-inflammatory cytokines). This work establishes a symmetric peptide scaffold as a versatile AMP platform, with RI8 showing promise for systemic MDR…
Read the paper
Related studies
- Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
- Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors
- Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy
- Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)
- GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.