Home Institution: Centro de Pesquisas Gonçalo Moniz, Fiocruz
U.S. Institution: UC Berkeley
Project Title: Identification of biomarkers that can be used to predict the development of active tuberculosis from latent infected people.
In 2012 an estimated 8.6 million people developed tuberculosis (TB) globally and 1.3 million people died from the disease. Of the 22 countries responsible for 82% of the total TB cases in the world, Brazil is ranked 17. Approximately 85,000 cases of TB are reported annually in Brazil (71,000 are new cases) and roughly 4,600 patients die of TB in Brazil per year. Until 2010, more than 5,000 new cases were reported in Bahia per year, designating Bahia as the 3rd state with the highest number of TB cases in Brazil, after São Paulo and Rio de Janeiro (Ministério da Saúde, Secretaria de Políticas de Saúde Brazil. DATASUS).
Exposure to M. tuberculosis can result in immediate bacteri
al clearance, the establishment of latent TB infection (LTBI), rapidly progressive disease, or reactivation disease. More than 90% of infected individuals do not develop active disease, however, their immune systems fail to eradicate the bacteria, which remain in a dormant state for life. For M. tuberculosis to remain inside a host for a prolonged period of time, it must control cell-wall lipid expression as a means to modulate the host immune response. We recently demonstrated that an M. tuberculosis strain disrupted in the mce1 operon, which encodes putative ABC transporters possibly involved in lipid importation through the cell-wall, has a diminished ability to express immunogenic lipids such as diacyltrehalose (DAT) and diacylated sulfoglycolipids (Ac2SGL). Lipid-induced host responses can be examined as biosignatures specific to M. tuberculosis infection. We propose to study such lipid-induced responses in order to identify new biomarkers that can be used to diagnose TB and to assess progression from LTBI to active disease in patients from Salvador, Bahia.
These are selected publications associated with the fellowship: