Mycobacterium tuberculosis remains the most successful human pathogen on the globe. One third of the world population is infected with TB, which is responsible for 3 million deaths annually. The rise of multi-drug resistant TB and the co-infection with HIV both add to the global concerns of effectively controlling TB in the coming millennium. The slow growth of M. tuberculosis confounds diagnosis and treatment and it takes several weeks for culture confirmation and drug susceptibility testing. The goal of Phase I study is to examine the feasibility of using advances in the MALDI-mass spectrometry developed at Sequenom Inc to determine whether this platform is amenable to rapid genotyping of rifampin resistance in M. tuberculosis. Representative mutations in the well-characterized rpoB gene will be used as a test system to evaluate the feasibility of extending this platform for high throughput genotyping against all known drug resistance genes. This proposal brings together the Sequenom DNA chip technology and the PHRI TB Center's expertise in the genetic characterization of M. tuberculosis and its large strain repository. PROPOSED COMMERCIAL APPLICATION: Commercial applications for determining drug resistance in clinical isolates of M. tuberculosis.