Strain-dependent disease progression and necrotizing granuloma formation in a murine model induced by virulent strains of <i>Mycobacterium avium</i> complex

The global incidence of pulmonary disease (PD) caused by non-tuberculous mycobacteria, particularly Mycobacterium avium complex (MAC), is increasing. However, the mechanisms underlying its pathological heterogeneity and variable treatment outcomes remain poorly understood. Here, we establish a murine model that recapitulates the key features of progressive MAC-PD, including necrotizing granuloma formation. We also demonstrate strain-specific differences in treatment responses despite comparable <i>in vitro</i> drug susceptibility. Notably, highly virulent strains induced necrotizing granulomatous lesions similar to those observed in patients with tuberculosis or MAC-PD. This study provides a valuable <i>in vivo</i> platform for investigating host-pathogen interactions, elucidating strain-dependent pathogenesis, and optimizing treatment strategies for MAC-PD.