Successful Treatment of Cutaneous <i>Acanthamoeba polyphaga</i> With Marine Algae, <i>Padina pavonica,</i> Extract: Targeting TLR2/TLR4 Signal and Cytokeratin 18 in Immunocompromised Animals

Cutaneous amoebiasis is a severe opportunistic infection, particularly prevalent among immunocompromised individuals, with high mortality due to the insidiousness of the disease, its ability to evade early diagnosis, and lack of specific symptoms. Herein, we aimed to evaluate the therapeutic potential of the marine alga, Padina pavonica, extract as a topical treatment for Acanthamoeba polyphaga skin infections. Immunocompromised mice with induced cutaneous lesions were topical infected with A. polyphaga and examined 3, 9, and 15 days post infection through histological and molecular analysis. Gas chromatography mass spectrometry of the P. pavonica extract exhibited 20 bioactive compounds belongs to steroids, fatty acids, carotenoid, and flavonoids. Infected animals exhibited ulceronecrotic, cellulitis, and intramuscular abscess involving the hind limbs. Moreover, dense inflammatory infiltrates, necrosis, and infiltration of Acanthamoeba trophozoites in dermal areas, sebaceous glands, around blood vessels, mixed with inflammatory cell infiltrate, and muscles were observed. Treatment with P. pavonica significantly accelerate wound healing, reduce inflammation, and restores normal skin architecture. Notably, P. pavonica extract enhances collagen deposition and modulated the expression of TLR2, TLR4, and cytokeratin 18 as key biomarkers of skin injury. These findings highlight, for the first time, the promising role of P. pavonica in managing wound healing and cutaneous acanthamoebiasis.