OR28

1:San Raffaele Scientific Institute

Pulmonary infections caused by nontuberculous mycobacteria (NTM) are gaining relevance as a major health concern, especially in individuals with conditions like chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. This rise in NTM infections emphasizes the urgent need for effective antimicrobial treatments, as NTM is often resistant to standard antibiotics. However, progress in developing novel therapies has been hampered by the absence of a standardized and representative murine model of chronic infection.

To address this limitation, we exploited the agar beads method to establish a chronic lung infection with Mycobacterium abscessus in immunocompetent mice.

In this model, NTM successfully induced a persistent lung infection with a stable and sustained bacterial load lasting up to two months with minimal systemic dissemination. Histopathological analysis of lung tissue, bacterial localization, and spatial transcriptomics data revealed that in chronically infected mice NTM co-localized with pathological areas, including tissues with infiltrating macrophages and granuloma-like structures, or submucosal inflammatory cells. Moreover, we recently demonstrated that this model can be effectively adapted to test clinical strains and used for the development of new antimicrobial strategies, including both pathogen-directed therapies (Lorè N.I. et al., 2023, ERJ 2023; Degiacomi G. et al., Int J Antimicrob Agents. 2024) and host-directed therapies (Poerio N. et al., Microbiol Spectr. 2022, unpublished).

In conclusion, our refined murine model of chronic lung infection by NTM provides valuable tools for advancing our understanding of bacterial pathogenesis and for evaluating the efficacy of novel antimicrobial therapeutic interventions against NTM lung infection.