Does infection progression of Mycobacterium abscessus depend on sex, age, and mouse strain?

The lack of a reliable chronic murine model limits drug evaluation against Mycobacterium abscessus. Existing models show discrepancies, especially regarding host factors such as mouse strain, sex, and age. To address this issue, we compared infection establishment and progression in BALB/cJRJ and C57BL/6NCrl mice across sexes and ages using a clinically relevant alginate bead-based model that mimics biofilm-like infection. BALB/cJRJ mice showed more sustained infection and lower variability, with no significant sex- or age-related differences. Based on these results, and taking into account the higher prevalence of nontuberculous mycobacterial pulmonary infections in female patients, as well as practical considerations, 5- to 6-week-old female BALB/cJRJ mice are appropriate for the M. abscessus bead model.IMPORTANCENontuberculous mycobacteria (NTM), including Mycobacterium abscessus, are increasingly recognized as opportunistic pathogens in humans. The urgent need for new anti-M. abscessus therapies is hindered by the lack of standardized and reproducible chronic murine infection models, as well as by discrepancies in the literature regarding the influence of host factors (mouse strain, sex, and age). Here, we systematically compared lung infections in the two most commonly used immunocompetent mouse strains, BALB/cJRJ and C57BL/6NCrl, across sexes and two age groups (5-6 vs 8-10 weeks), using the alginate-beads infection model. We identified 5-to 6-week-old female BALB/c mice as the most suitable conditions for implementing the M. abscessus beads model, providing more sustained infection and lower variability. Our findings clarify the impact of host-related variables and provide guidance for improving the standardization and reproducibility of murine models used in preclinical evaluation of anti-NTM therapies.