Matrixyl-derived hybrid peptide 3.1-PP4 shows potent antibacterial and antibiofilm activity against multidrug-resistant Gram-negative bacteria.

Antimicrobial resistance is a severe global health threat, particularly from multidrug-resistant (MDR) Gram-negative bacteria known as ESKAPE pathogens (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa). These bacteria are frequently isolated from severely infected skin lesions like diabetic foot ulcers (DFU), complicating wound management and increasing risks for procedures like surgery and transplantation. Current antibiotics are often ineffective against these pathogens, creating an urgent need for novel treatments. This research explores hybrid peptides that combine antimicrobial action with wound-healing properties, aiming to create a dual-effect topical agent that can both clear infections and promote tissue repair in chronic, infected wounds.

Researchers synthesized a novel hybrid peptide, 3.1-PP4, by combining an antimicrobial motif with the collagenesis-inducing peptide C16-PP4 ("Matrixyl"). Its efficacy was tested in vitro. Minimum Inhibitory Concentrations (MIC) were determined against standard strains of Escherichia coli and Pseudomonas aeruginosa, as well as against multidrug-resistant clinical isolates of Klebsiella pneumoniae, E. coli, and P. aeruginosa. The peptide's effect on biofilm formation and disaggregation was assessed on K. pneumoniae. Cytotoxicity was evaluated using HFF-1 human fibroblast cells. Finally, its ability to induce collagenesis was compared to the reference peptide, Matrixyl.

The hybrid peptide 3.1-PP4 demonstrated potent antimicrobial activity with MIC values as low as 1.0 μM against Escherichia coli and 2.1 μM against Pseudomonas aeruginosa. It exhibited low toxicity to HFF-1 human fibroblasts, indicating a favorable safety profile for topical use. Crucially, the peptide was also highly effective against multidrug-resistant clinical isolates.

MIC values against MDR strains of Klebsiella pneumoniae, E. coli, and P. aeruginosa ranged between 0.5 μM and 4.1 μM. Furthermore, 3.1-PP4 successfully hampered the formation of and disaggregated existing biofilms of resistant K. pneumoniae isolates. Importantly, the peptide retained the collagenesis-inducing behavior of its parent compound, C16-PP4 ("Matrixyl"), confirming its dual-action potential for both fighting infection and promoting healing.