Mycobacterium tuberculosis signal transduction system required for persistent infections

It is estimated that nearly 2 billion people currently suffer from latent M ycobacterium tuberculosis infection. Although the key front-line antituberc ulosis drugs are effective in treating individuals with acute tuberculosis, these drugs are ineffective in eliminating M. tuberculosis during the pers istent stages of latent infection. Consequently, therapeutics that directly target persistent bacilli are urgently needed. We have conducted a global analysis on a group of regulatory determinants that may play a role in M. t uberculosis virulence, and identified a two-component response regulator wh ose expression is required for entrance into and maintenance of persistent infection. Inactivation of this response regulator, Rv0981 (termed here mpr A for mycobacterial persistence regulator), affected M. tuberculosis H37Rv growth in vivo in an organ- and infection stage-specific fashion. These res ults indicate that two-component systems are important for adaptation of th e tubercle bacillus during stages of persistent infection.