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

Abstract

Objectives: 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 Pseudomonas aeruginosa under immunosuppression. Methods: Male BALB/c mice (22–24 g) were immunocompromised with cyclophosphamide. Three days later, full-thickness excisional wounds were created and infected with P. aeruginosa (107 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. Results: Lysin GRC-ML07 induced bacterial lysis accompanied by low activation of TLR2, TLR4, or TLR7/8 signaling pathways and pro-inflammatory cytokine production in vitro. Its application in vivo 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. Conclusions: 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.

Affiliated Institutions

• Joint Institute for High Temperatures RU
• Sechenov University RU
• Ministry of Health of the Russian Federation RU
• Pirogov Russian National Research Medical University RU

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