The Antimicrobial Peptide, Dermaseptin DMS-DA6, a Promising Alternative to Conventional Antibiotic in the Treatment of N. brasiliensis-Induced Actinomycetoma.

Actinomycetoma is a chronic infectious disease recognized by the World Health Organization as a neglected tropical disease. In the Americas, the most common etiologic agent is the Gram-positive bacterium, Nocardia brasiliensis. This pathogen is a facultative intracellular organism that can multiply and survive within macrophages, evading microbicidal mechanisms by inducing an immunosuppressive environment. Current antibiotic treatments are expensive, prolonged and toxic, and bacterial resistance has been reported. Host defense peptides, known for their bactericidal and immunomodulatory properties, represent a promising new therapeutic approach. Recently, DMS-DA6, a dermaseptin isolated from the Mexican tree frog, Pachymedusa dacnicolor, has been shown to exert strong activity against Gram-positive bacteria, including multidrug-resistant strains. Our study evaluated the effects of DMS-DA6 in a mouse model of actinomycetoma caused by N. brasiliensis, comparing it with the conventional antibiotic linezolid. Infected mice were treated either twice a week with this peptide at a dose of 12.5 mg/kg or every 12 h with linezolid at a dose of 25 mg/kg over a four-week period. Our results suggest that DMS-DA6 is more effective at resolving the disease than linezolid, as it achieves a similar reduction in inflammation and bacterial load of the footpad at a lower dose and with fewer injections. Furthermore, DMS-DA6 modulates IL-10, IL-1α, and IL-6 levels at the chronic stage of actinomycetoma infection and increases the abundance of CD4 + and CD8 + T lymphocytes in the infected footpad. These findings highlight the potential of DMS-DA6 as an innovative addition to current treatments.