In Vitro Model of Hypoxically Induced Nonreplicating Persistence of Mycobacterium tuberculosis

Great progress has been made in the latter half of the twentieth century in the understanding of the immunology of tuberculosis and of strategies for chemotherapeutic management of this disease. Indeed, given the evidence that the dominant, and perhaps sole, ecologic niche of Mycobacterium tuberculosis is the infected human host, it seemed reasonable to hope that the disease could not only be controlled, but eradicated by the end of this century (). These hopes are dashed by the periodic resurgence of tuberculosis in various populations. Undoubtedly socioeconomic factors have played a major role in the failure to eradicate this disease, but another, neglected, factor is the apparent ability of the tubercle bacillus to remain in a relatively quiescent state in the host, neither replicating and causing progression of disease, nor dying off and disappearing from the host’s tissues, in spite of apparently adequate immune responses and aggressive chemotherapy.