Inhibitory effect of tetracycline and doxycycline on resistance of mice to infection with a tetracycline-resistant strain of Listeria monocytogenes.

By transposon mutagenesis a tetracycline-susceptible strain of Listeria monocytogenes (MIC 1 mg/l. for tetracycline and 0.25 mg/l. for doxycycline) was rendered resistant (MIC 64 mg/l. for tetracycline and 16 mg/l. for doxycycline). Infection of mice with this resistant strain led to an acute infection. Treatment with 2 x 2 mg tetracycline per day did not influence the course of infection during the first 3 days, indicating that the nonspecific resistance, mediated mainly by macrophages and granulocytes, was not affected by this treatment. The second phase of infection, characterized by a continuous resistance to infection due to macrophages activated by T-lymphocytes was, however, definitely hampered. Even acquired immunity to a secondary infection was impaired by treatment with tetracycline, indicating that cell-mediated immunity can be blocked. The course of infection of athymic, nude mice which are unable to build up a cell-mediated immune response, was not affected by tetracycline treatment. Doxycycline expressed the same activities as tetracycline.