Design, synthesis, and evaluation of membrane-targeted resveratrol-antimicrobial peptide mimic conjugates for MRSA-infected wound healing.

Development of Novel Antimicrobial Peptides and Their Engineering into Nanoparticles to Improve Performance

Antimicrobial peptides (AMPs) are promising alternatives to antibiotics, but discovering potent, low-toxicity candidates and improving their delivery remain challenging. In this study, novel AMPs were identified by constructing and screening a synthetic random peptide library using a bacterial surface display system. Rational design generated derivative peptides, among which WP-4 and WP-6 showed high antimicrobial activity, good biocompatibility, rapid bactericidal effects, and low propensity for resistance development. WP-6 also showed good in vivo therapeutic potency in a murine Escherichia coli systemic infection model. Mechanistic studies indicated that WP-4 and WP-6 target bacterial cell membranes, disrupt the proton motive force, and induce excessive reactive oxygen species accumulation. To further improve their activity and in vivo performance, WP-4 and WP-6 were encapsulated within zeolitic imidazolate framework-8, yielding improved antimicrobial activity and proteolytic resistance. These nanoparticles exhibited superior therapeutic efficacy in a Streptococcus suis-induced arthritis model. Our study identified potent AMPs with promising therapeutic potential.

A multifunctional molecular platform for restoration quinolone antibiotics: synthesis, antimicrobial, anti-biofilm and preliminary mechanistic studies.

Ruthenium complexes as potent antibiotics in methicillin-resistant Staphylococcus aureus (MRSA) via membrane damage.

With the growing crisis of multidrug-resistant bacterial infections, a series of novel ruthenium complexes were rationally designed and synthesized to disrupt the integrity of bacterial membranes. In vitro antibacterial screening demonstrated that the lead compound Ru-6 possesses potent bactericidal activity against multiple methicillin-resistant Staphylococcus aureus (MRSA) isolates, with minimum inhibitory concentrations (MICs) ranging from 1.56 to 6.25 μg/mL. Concurrently, Ru-6 displayed negligible hemolytic toxicity toward rabbit erythrocytes. Mechanistic studies suggest that Ru-6 exerts its antibacterial effects through a dual-pathway mechanism: phosphatidylglycerol (PG) acts as a potential membrane interaction partner for Ru-6, facilitating bacterial membrane damage; and also Ru-6 treatment triggers elevated reactive oxygen species (ROS) levels, which is speculated to mediate subsequent intracellular injury. Transcriptomic analysis further revealed that Ru-6 modulates the regulation of bacterial internal genes. In vivo experiments (mouse skin wound infection and Galleria mellonella infection models) confirmed that Ru-6 effectively eradicates MRSA without significant toxicity to host tissues. Ru-6 exhibits considerable potential as a novel antimicrobial agent for clinical application.

Design of a cyclic peptide targeting intracellular Staphylococcus aureus

Findings identify cyclotide grafting as a strategy to improve peptide stability and intracellular delivery, and support MCo-KTR2 as a scaffold for further optimization against intracellular MRSA infections.

Dual-Mechanism Antimicrobial Peptides from a Nature-Inspired Scaffold

It is demonstrated how targeted sequence refinement can substantially enhance antimicrobial potency while modulating interactions with bacterial membranes and the transcription/translation machinery.

Development and Biological Evaluation of FL18-Based Novel Antimicrobial Peptide Constructs Against Bacterial Pathogens

Antimicrobial resistance has become a serious global health challenge, increasing the need for new therapeutic strategies beyond conventional antibiotics. In this study, FL18 and its chimeric derivatives, FL18–TAT8 and FL18–Ahx–TAT8, were designed to combine antimicrobial activity with the cell-associated advantages of a cell-penetrating peptide motif and were synthesized by Fmoc-based solid-phase peptide synthesis. Their molecular masses were confirmed by MALDI-MS analysis. The antibacterial activities of the peptides were evaluated against representative Gram-negative and Gram-positive bacterial strains, including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecium. The tested peptides exhibited minimum inhibitory concentration values in the range of 4–64 μM depending on the peptide sequence and bacterial strain, while TAT8 alone showed no significant antibacterial activity under the tested conditions. Among the constructs, FL18–Ahx–TAT8 displayed the most favorable overall antibacterial profile, particularly against P. aeruginosa and E. faecium. Biocompatibility studies further showed that FL18 and its chimeric derivatives maintained approximately 75–90% HaCaT cell viability across the tested concentration range and exhibited generally low hemolytic activity. In addition, confocal microscopy and flow cytometry revealed peptide-associated fluorescence in HaCaT cells, with the TAT8-containing chimeras showing a broader and more pronounced fluorescence distribution than FL18 alone. Overall, these findings demonstrate that FL18-based chimerization provides a modular and effective strategy for tuning antibacterial activity, biocompatibility, and peptide–cell interaction behavior, underscoring their promise as building blocks for the design of next-generation antimicrobial peptide platforms.