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. <i>Mycobacterium abscessus</i> 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 <i>Mycobacterium abscessus</i> and <i>M. massiliense</i>. Agelaia-12 showed a minimum inhibitory concentration (MIC) of 25 μM detected against <i>M. abscessus</i> and <i>M. massiliense</i> 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 <i>M. abscessus</i> exhibited altered dye accumulation after treatment with Agelaia-12. Treatment of <i>M. abscessus</i>- or <i>M. massiliense</i>-infected murine macrophages with Agelaia-12 decreased the mycobacterial load by 92% for the tested strains. Additionally, IFN-y KO mice infected with <i>M. abscessus</i> or <i>M. massiliense</i> 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.