Mouse model of pulmonary disease after aerosol infection with mycobacterium xenopi

Rationale: Opportunistic respiratory infections due to M. xenopi are on the rise in industrialized countries and current therapies are inadequate. Only two experimental studies with the beige and Swiss mouse models iv-infected have been performed so far. As aerosol inhalation is the probable route of infection in humans, we hypothesized that aerosol infection of mice would better recapitulate human infection and permit better assessment of the response to antibiotic treatment. Our first objective was to determine which strain of mice was the most susceptible to aerosol infection. Methods: Four strains of mice were tested: BALB/c, C57Bl/6, Beige, and athymic nu/nu (Nude). For each strain, thirty 6-week-old females were simultaneously aerosol infected with 4.7 log10 of M. xenopi ATCC # 19971. At 1, 2, 3, 4, 8, 12 and 23 weeks post-infection, three mice per group were sacrificed for gross lung lesions, spleen weight, and lung and spleen CFU counts. From week 4 to 12, 9 mice of each group were treated with clarithromycin 100 mg/kg/d 5 days a week. Three treated mice per group were sacrificed at week 8 and 12. Results: In BALB/c, C57Bl/6, Beige and Nude mice infected with M. xenopi , the lung CFU counts steadily increased to reach 5.57, 5.92, 5.99, and 5.75 log10, respectively at week 4; 6.35, 6.72, 6.60 and 6.93 log10, respectively at week 8; 6.51, 6.43, 7.69, and 6.63 log10, respectively at week 12; and 6.59, 6.72, 8.16, 7.32 log10, respectively at week 2. In all mice, M. xenopi disseminated to the spleen. Clarithromycin treatment reduced significantly, by 2 log10, the lung CFU counts in all strains of mice. Conclusion: Nude mice were the most susceptible to aerosolized M.xenopi infection.