In the classical concept of tuberculosis infection (TBI), M. tuberculosis bacteria are believed to survive for years at the site of the original infection in the lung and draining lymph nodes and in the small granulomas or solid caseous material of lympho-hematogenously seeded foci. Presumably, local conditions, an intact cell-mediated immunity or the presence of inhibitors result in conditions unfavorable to replication. Recent mapping of the complete genome sequence of the bacterium demonstrates that the organism has the potential to synthesize enzymes involved in anaerobic metabolism.72 Although rapid death and autolysis occur after abrupt depletion of oxygen, the organism can shift into a state of dormancy if exposed to gradual reductions in oxygen tension.73,74 Therefore, although M. tuberculosis thrives in an aerobic environment, it possesses the genetic and biochemical capability to survive anaerobically in experimentally oxygen-depleted media. Granuloma formation, with its oxygen-depleted environment, is a defining characteristic of TB. It is this stage of infection that is termed TBI and is usually identified by a positive TST or IGRA in the absence of active disease (see Chapter 4: Diagnosis of Tuberculosis Infection).
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