Efficacy of LNT103 against Pseudomonas aeruginosa in an ex vivo porcine corneal infection model

Canine bacterial keratitis is a predominant ocular disease in veterinary practice, with Pseudomonas aeruginosa serving as a primary causative pathogen of ulcerative keratitis (melting ulcers). The widespread emergence of multidrug-resistant P. aeruginosa strains underscores an urgent clinical need for novel therapeutic alternatives. The antimicrobial efficacy and histopathological impact against P. aeruginosa were evaluated using endolysin LNT103, a novel genetically engineered bacteriophage-derived enzyme, in a porcine ex vivo corneal infection model. A superficial anterior lamellar keratectomy was performed on fresh porcine corneoscleral rims (CSRs) to simulate ulcerative keratitis. Corneas were inoculated with Pseudomonas aeruginosa ATCC 15692. Six groups were established: negative control, positive control, ampicillin (256 µg/mL), amikacin (8 µg/mL), high-dose LNT103 (8 µg/mL), and low-dose LNT103 (2 µg/mL). Treatments were applied topically every 12 h for 60 h. Efficacy was assessed via gross inspection, bacterial colony enumeration (Log 10 CFU/mL) and histopathological analysis with Gram staining. The MIC of LNT103 was determined as 4 µg/mL. High-dose LNT103 and amikacin significantly reduced viable bacterial counts compared to the positive control and ampicillin groups ( p < 0.05). Histopathology confirmed that high-dose LNT103 effectively eradicated bacterial infiltration within the corneal stroma, whereas the low-dose and ampicillin groups showed persistent Gram-negative bacilli and structural colonization similar to the untreated infected group. Endolysin LNT103 demonstrates potent, dose-dependent antimicrobial activity against P. aeruginosa in corneal tissue. These findings suggest that LNT103 is a promising non-antibiotic therapeutic candidate for treating refractory or multi-drug resistant canine bacterial keratitis.