Senior Scholar Award in Global Infectious Disease
Lee W. Riley, M.D.
University of California - Berkeley

Mycobacterium Tuberculosis Latency and Reactivation Tuberculosis

After AIDS, tuberculosis (TB) is the most common infectious cause of death in adults worldwide. One-third of the world’s population is infected with the organism Mycobacterium tuberculosis that causes TB. One can develop TB shortly after an infection, but most new TB cases in the world arise from those who are chronically infected with the organism. Thus preventing those who are already infected from developing active disease (reactivation TB) will significantly reduce the worldwide burden of TB.

How M. tuberculosis establishes this chronic infection (latency) in the human host is not understood. Even though drugs exist to treat TB, they are not highly effective against organisms that remain dormant in the human host. This is why TB has to be treated anywhere from 6 to 18 months with multiple drugs. The difficulties of treatment also contribute to the development of drug-resistant form of TB, which is even more difficult and expensive to treat. Therefore, understanding how M. tuberculosis establishes latency is a major priority in TB research.

We have identified a set of genes in M. tuberculosis that allows it to establish this chronic infection (latency). These genes are all located in a cluster of genes called the mce operon. The evidence we have that these genes may be involved in latency is that when we disrupt these genes, the mutant organism becomes unable to establish a long-term infection in the mouse model of TB. We wish to analyze these genes to understand how this organism establishes latency. We believe that targeting the products of these genes may lead to the identification of a new vaccine or new drugs that will prevent the organism from successfully establishing latent infection. Furthermore, such reagents may be used to treat or prevent those who are already infected from ever developing TB—practically one-third of the world’s population. Finally, what we learn about the mechanism of latency in TB may apply to many other infectious diseases that are difficult to treat because of their respective infectious agents’ propensity to cause chronic infections.

Contact Dr. Riley.