a Slow-Growing Strain That Persists in Host Tissues

The in vivo rate of proliferation of Mycobacterium tuberculosis, the causative agent of tuberculosis, has been linked to the rate of progression and severity of disease. Here, we report that deletion of the gene MT2175 (Rv2115c), a putative mycobacterial proteasome–associated AAA-ATPase, leads to a reduction in the growth rate of M. tuberculosis in vitro and in vivo. Despite the reduced growth, the mutant persisted, with slow and gradual clearance in mouse lungs. The mutant elicited reduced levels of interferon-g production in the lungs and, when used as an immunizing agent, provided significant protection against challenge with a virulent strain of M. tuberculosis. Expression of the genes lat and MT3159 were highly up-regulated in the mutant. Thus, loss of MT2175 slows both in vitro and in vivo growth rates and compromises the lethality of M. tuberculosis in mice but has a minimal impact on the organism’s ability to persist in host tissues. Mycobacterium tuberculosis, the etiological agent of tu-berculosis (TB), is one of the deadliest pathogens known to humans and kills ∼2–3 million people each year [1]. The recent emergence of multidrug-resistant strains de-tected in prisons around the world and the reactivation of latent TB bacilli in the HIV-infected population ha