Course of murine tuberculosis and response to first-line therapy depends on route of infection and inoculum size

BACKGROUND: In the search for new anti-tuberculosis drugs, numerous potential drugs are being screened in vitro. In animal models, promising new anti-tuberculosis drugs are assessed in terms of toxic side effects and comparative therapeutic efficacy. Mice are frequently used and experimental infections are established in different ways. OBJECTIVE: To investigate to what extent the route of Mycobacterium tuberculosis inoculation is a determinant in the pathogenesis of tuberculosis (TB) and the therapeutic outcome. Results will contribute to insight into the translational value of TB models used for preclinical studies. DESIGN: TB in mice was established through intratracheal or intravenous mycobacterial inoculation. The efficacy of a 26-week treatment regimen was evaluated, including assessment of relapse of infection 13 weeks post-treatment. RESULTS: It was shown that the course of TB and the therapeutic response, in terms of histopathological characteristics and mycobacterial load, in lungs and extrapulmonary organs is substantially different and dependent on the route of infection applied and the inoculum size used. CONCLUSION: When evaluating the comparative therapeutic potential of novel anti-tuberculosis drugs or drug treatment schedules investigated in different studies, it should be noted that the route of infection applied and the inoculum size used influence the course of murine TB and the therapeutic response to the standard firstline anti-tuberculosis drug regimen.

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