Mycobacterium tuberculosis Adaptation to Survival in a Human Host

Mycobacterium tuberculosis exists exclusively as a pathogen of humans and in some cases of animals. It is not thought to exist in the environment other than for brief periods during transfer from an infected host to an uninfected contact. Thus M. tuberculosis must adapt to an in vivo environment by modifying gene expression. Differential expression can occur in immune cells such as macrophages, larger immune structures such as granulomas, and within liquefied lesions of the lung. Within the human body tubercle bacilli experience reactive oxygen intermediates as well as acidity within the phagosomes of macrophages. In addition within the centers of caseating granulomas bacilli experience low oxygen tension as well as toxic lipases and proteases released by dead immune cells. High temperature is present within the body of a person with active tuberculosis in the form of a fever. There may be other unrecog‐ nized signals and stresses that modulate gene expression within invading M. tuberculosis bacilli as well. Examination of gene expression during in vivo growth, within macrophages, or during application of specific stresses can illuminate which critical pathways in the mycobacterium are upregulated that lead to an M. tuberculosis bacillus exquisitely adapted to in vivo survival.