Novel Synthetic Peptide Agelaia-12 Has Improved Activity Against Mycobacterium abscessus Complex

Fast-growing mycobacteria cause difficult-to-treat infections due to their high intrinsic resistance to antibiotics as well as disinfectant agents. Mycobacterium abscessus complex (MAC) is the main cause of nontuberculous mycobacteria diseases. In this work, we evaluated the activity of the novel synthetic antimicrobial peptide, Agelaia-12, against Mycobacterium abscessus and M. massiliense. Agelaia-12 showed a minimum inhibitory concentration (MIC) of 25 μM detected against M. abscessus and M. massiliense with no cytotoxicity. The scanning electronic microscopy analysis of mycobacterial treated with Agelaia-12 demonstrated the presence of filamentous structures and aggregation of the cells. Congo red binding assay of M. abscessus exhibited altered dye accumulation after treatment with Agelaia-12. Treatment of M. abscessus- or M. massiliense-infected murine macrophages with Agelaia-12 decreased the mycobacterial load by 92% for the tested strains. Additionally, IFN-y KO mice infected with M. abscessus or M. massiliense and treated with Agelaia-12 showed a 98% reduction in lung bacterial load. Thus, the synthetic peptide Agelaia-12 may be a promising biomolecule for the treatment of mycobacteriosis, and its structural properties may serve as a foundational model for the design and development of novel pharmaceutical agents aimed at combating this disease.