LIMITS IN TUBERCULOSIS CHEMOTHERAPY AS REVEALED BY EXPERIMENTAL STUDY IN MICE

Abstract

Viable forms of tubercle bacillus, even when they are essentially drug-sensitive, can persist in mouse tissue under the treatment with antituberculous drugs. This peculiar phenomenon characteristics of the chronic stage of infection is called “microbial persistence”. To explain the underlying mechanism, some model experiments were conducted. Infection with resting bacilli was attained in mice with a streptomycin-dependent strain having completed residual growth on the medium lacking the antibiotic. Isoniazid administration failed to eliminate such resting bacilli from the mouse tissue. An additional experiment showed that the challenge inoculum whose multiplication was inhibited by vaccine-induced immunity did not respond satisfactorily to the mycobactericidal action of isoniazid. These observations and others led us to a view that microbial persistence results from the insensitiveness to chemotherapeutics of the bacilli in a resting condition under the pressure of infection immunity.