In vivo imaging identified efficient antimicrobial treatment against Mycobacterium marinum infection in mouse footpads

Abstract

Abstract Mycobacterium marinum (M. marinum) is the most common causative bacteria of cutaneous non-tuberculous mycobacterial (NTM) infections, including fish tank granuloma. Treating M. marinum-caused infection takes longer than other NTM diseases because M. marinum is less susceptible to antimicrobial agents. A standard treatment regimen for M. marinum infection has not been established yet, and few in vivo experiments have been performed in mammals to evaluate the bactericidal effects of antimicrobials. In this study, we developed a noninvasive in vivo imaging method to assess the therapeutic efficacy of antimicrobials against M. marinum infection. The data obtained using fluorescent protein or bioluminescence from luciferase will offer valuable insights into bacteria visualization across various bacterial infections. Furthermore, through this imaging technique, we demonstrated that combining clarithromycin, rifampicin, ethambutol, and minocycline effectively cleared M. marinum from the footpad. Granulomas with necrotic abscesses formed on the footpad of M. marinum-infected mice, primarily due to neutrophils involved in the host’s cell-mediated immune response. Inflammatory cytokine and chemokine levels significantly increased 7 days post-infection, aligning with the footpad swelling and granuloma formation observed in the untreated group. Interestingly, immune mediators and cells induced by M. marinum footpad infection were crucial factors associated with hypersensitivity and granuloma formation, as seen in pulmonary tuberculosis. This novel imaging analysis using a cutaneous NTM mouse model might be a powerful tool for the comprehensive analysis of mycobacterial infections.