There are only few reports on the virulence of isoniazid (INAH) resistant tubercle bacilli in mice, although many evidences have been accululated that INAH resistant tubercle bacilli will manifest loss of virulence for guinea pigs. The present paper deals with the virulence for mice and the catalase activity of INAH resistant tubercle bacilli.
Of 7 INAH resistant strains used in the present study, 4 were isolated from the sputa of tuberculous patients, treated with INAH, and the other 3 strains were obtained in vitro by culturing H37Rv under the selection by INAH. Each of these INAH resistant strains revealed various degrees of resistancy some were completely or partially resistant to higher concentrations of INAH, and the others were partially or completely resistant to rather
lower concentrations of INAH.
20 mice were provided for the virulence test of each strain. Standardized suspension containing approximately 0.1 mg wet weight of test organisms was inoculated to the mice intravenously. The inoculated mice were divided into 2 groups. One group of them served for the calculation of survival rate, and 3 mice in the remaining group were sacrificed for autopsy every 10 days after infection, in order to search the infectioe agents in the internal organs and to examine the gross pathological findings.
Cultures obtained from the sacrificed animals were retested for their INAH resistance to see the changes of INAH resistance in vivo, occurred during the course of the infection, if any. Catalase activity of these cultures were also tested by pouring H
2O
2 solution.
The known 0isoniazid susceptible strain was always served as the controls in each set of the tests.
The results obtained are as follows:
1) Judged from the survival rate, results of the cultivation and gross pathological findings of infected animals, all of the INAH resistant strains tested, whether they were isolated from patients or obtained in vitro under the serection by INAH, showed much the same virulence for mice as the control INAH susceptible strain.
2) Results of INAH resistance tests of the cultures obtained from sacrificed mice showed that the partially INAH resistant strains revealed the tendency of decreasing their INAH resistante during the course of infection, while the completely INAH resistant strains maintained the same degree of resistance throughout the course of infection.
3) The completely INAH resistant strains manifested loss of their catalase activity, while the partially INAH resistant strains showed weak to moderate catalase activity.
The results shown in (2) and (3) indicate that so-called partially INAH resistant strain has the tendency to revert to INAH sensitive nature, hence its conposition of population is always not homogeneous, while so-called completely INAH resistant strain has the population of homogeneous composition. It will be important in the study of drug resistance to consider such composition of population.
From the results shown in (1) and the accumulating evidences indicating the loss of virulence in guinea pigs of INAH resistant tubercle bacilli, it will be concluded that virulence of INAH resistant tubercle bacilli should be determined by the species of infected host. It will be very dangerous to consider that INAH resistant tubercle bacilli may be attenuated for human similarly for guinea pigs.
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