Journal Article

Wound-Healing Potential of Engineered Lysin GRC-ML07 in Pseudomonas aeruginosa Infected Wounds in Immunocompromised Mice

Litvinenko, Veronika, Guseva, Tatiana, Vasina, Daria, Guschin, Vladimir, Slonova, Darya, Abdulkadieva, Mariam, Mazunina, Elena, Antonova, Nataliia, Sysolyatina, Elena, Sobyanin, Konstantin, Gintsburg, Alexander, Parshina, Olga, Domnin, Pavel, Poloskov, Vladislav

2025

Overview

The study aimed to evaluate the antibacterial and wound-healing potential of the engineered lysin GRC-ML07 in a mouse model of full-thickness wounds infected with multidrug-resistant under immunosuppression. Male BALB/c mice (22-24 g) were immunocompromised with cyclophosphamide. Three days later, full-thickness excisional wounds were created and infected with (10 cells/wound). The lysin GRC-ML07 incapsulated into an alginate gel was applied topically to the wound area twice a day for four days after infection. Wound swabs for microbiological assays and scab tissues for cytokine and cellular profiling were collected on days 4 and 7. Histological samples were taken on days 4, 7, 14, and 21. Lysin GRC-ML07 induced bacterial lysis accompanied by low activation of TLR2, TLR4, or TLR7/8 signaling pathways and pro-inflammatory cytokine production . Its application resulted in decreased levels of GM-CSF, IL-1β, IL-6, IL-17A, and TNF-α in the wound, accompanied by a 46% increase in neutrophil counts on day 4 compared to control and placebo (alginate gel) groups. By day 7, lysin treatment reduced bacterial load by 2 log, decreased neutrophil counts in wounds, and led a transition of the wounds to the granulation and epithelialization phase with scab desquamation. It was first shown that engineered lysin GRC-ML07 exhibits not only antibacterial, but pronounced pro-healing effects in immunocompromised mice, promoting resolution of inflammation and transition to the granulation/epithelialization phase.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Agonists / Alginates / Alginic acid / Analysis / Antibacterial agents / antibacterial effect / Antiinfectives and antibacterials / Antimicrobial agents / B cells / Bacteria / Biofilms / Cyclophosphamide / Cytokines / Cytotoxicity / Enzymes / Granulation / Granulocyte-macrophage colony-stimulating factor / Health aspects / immune suppression / Immunosuppression / Immunotherapy / Infection / Infections / Inflammation / Leukocytes (neutrophilic) / Ligands / lysin / Microbiological assaying / Microbiology / mouse model / Multidrug resistance / Pathogens / Pseudomonas aeruginosa / Thickness / TLR2 protein / TLR4 protein / TLR7 protein / Toll-like receptors / Tumor necrosis factor-α / Wound healing / Wound infection