Latent Tuberculosis and Active Tuberculosis Disease Rates among the Homeless, New York, New York, USA, 1992–2006

We conducted a retrospective study to examine trends in latent tuberculosis infection (LTBI) and TB disease rates among homeless persons in shelters in New York, NY, 1992–2006. Although TB case rates fell from 1,502/100,000 population to 0, a 31% LTBI rate in 2006 shows the value of identifying and treating TB in the homeless

Whole cell screen for inhibitors of pH homeostasis in Mycobacterium tuberculosis

Bacterial pathogens like Mycobacterium tuberculosis (Mtb) encounter acidic microenvironments in the host and must maintain their acid-base homeostasis to survive. A genetic screen identified two Mtb strains that cannot control intrabacterial pH (pHIB) in an acidic environment; infection with either strain led to severe attenuation in mice. To search for additional proteins that Mtb requires to survive at low pH, we introduced a whole-cell screen for compounds that disrupt pHIB, along with counter-screens that identify ionophores and membrane perturbors. Application of these methods to a natural product library identified four compounds of interest, one of which may inhibit novel pathway(s). This approach yields compounds that may lead to the identification of pathways that allow Mtb to survive in acidic environments, a setting in which Mtb is resistant to most of the drugs currently used to treat tuberculosis