**14. Summary**

As mycobacteria invade their human hosts they must respond to a plethora of stresses many of which are generated by the host's immune system. Under this selective pressure, *M. tuberculosis* has evolved mechanisms to combat the toxic insults of the host. Although myco‐ bacteria are inherently resistant to environmental stresses due to their thick waxy cell envelope, upregulation of genes further reinforce this defense. In addition there are proteins upregulated by environmental stressors which can detoxify the mycobacterial cell as is the case of acidic stress and upregulation of ammonia extruding pumps that neutralize acidic pH of the macrophage phagosome. Thus inducible systems allow *M. tuberculosis* to resist environmental stresses and persist in the human body to cause active or latent disease.

Understanding the specific steps in infection, the stresses associated with each step, and the mycobacterial response may be of clinical relevance. The knowledge that oxidative stress and acidic stress may predominate as adaptive immunity makes the host's macrophages more activated, may lead to the development of chemotherapeutic agents that target mycobacterial components produced by these stressors during this infective stage. In addition, the knowl‐ edge that mycobacteria may utilize toxin-antitoxin systems to slow their growth and to enhance their innate antibiotic resistance may spur the development of therapies that target these systems which could be used in conjunction with traditional antibiotic treatments. Chemotherapeutic agents given to decrease activity of triacylglycerol synthase may decrease infectivity of sputum positive individuals by inhibiting lipid body production in the bacilli while antibiotic treatment lags in its sterilizing activity. Ultimately treatments may be devel‐ oped which target inducible systems upregulated by stresses, and may interfere with myco‐ bacterial responses to these stressors. By thwarting these adaptive responses potentially with chemotherapeutic agents, mycobacteria may be rendered more fragile and susceptible to the host's immune system. In addition a greater understanding of how *M. tuberculosis* enters a latent state of persistence could lead to treatments that prevent this microbe from reactivating from the dormant state, or from becoming dormant to begin with. Greater understanding of *M. tuberculosis* responses to *in vivo* growth will hopefully lead to the development of technol‐ ogies that lessen *M. tuberculosis'* global impact on human health.
