Tuberculosis

Simon Spivack, Albert Einstein College of Medicine in the U.S. will test the theory that DNA of the Tuberculosis bacterium can be detected in exhaled breath. The team will capture exhaled breath condensate samples via a non-invasive device and use nucleic acid amplification to detect the presence of mycobacteria.

Vineet Gupta of the University of Miami in the U.S. will develop a computational model to identify new DNA sequences in the Tuberculosis bacterium that can be used as biomarkers, and then employ zinc-finger tags to detect the identified DNA sequence in a diagnostic test.

Ranjan Nanda and Virander Chauhan of the International Centre for Genetic Engineering & Biotechnology in India will gather breath samples from tuberculosis patients and use gas chromatography-mass spectrometry (GC-MS) to identify and track unique molecules such as volatile organic compounds (VOCs) that might serve as biomarkers to diagnose tuberculosis. The overall goal is to then create a handheld "electronic nose" to diagnose the disease in resource-poor settings.

Scott Phillips, of Pennsylvania State University in the U.S. proposes to develop a polymer reagent to be deposited at the bottom of a small paper cup used to collect a sputum sample, where it will detect proteins secreted by tuberculosis and turn indicate TB-positive samples by changing color.

Johnjoe McFadden of the University of Surrey in the United Kingdom will modify the BCG vaccine currently used against bovine and human tuberculosis, and develop a complementary diagnostic test that can distinguish between tuberculosis infection and vaccination. BCG is the only effective tuberculosis vaccine, however it interferes with diagnostic tests, preventing the distinction between infection and vaccination, which is important for control efforts in developing countries.

William Royea of Next Dimensions Technology, Inc., in the U.S. seeks to develop a point-of-care breath analyzer. The proposed system aims to use an array of chemical films that are sensitive to changes in electrical conduction as a result of volatile organic compounds (VOCs) produced by tuberculosis (TB). In this project's Phase I research, Royea and his team demonstrated proof-of-concept for detecting breath-based biomarkers of TB in a clinical setting.

To test the theory that certain metabolic pathways essential to the survival of bacteria are immutable and therefore promising targets of drug therapy, Krishna Kodukula and colleagues at SRI International in the U.S. will identify peptides that bind key metabolites of M. tuberculosis, and test their ability to kill the bacteria.

Marcus Horwitz and colleagues at UCLA in the U.S. will develop and test a novel drug delivery system in which nanoparticles loaded with anti-TB drugs selectively target macrophages, and release the drugs intracellularly via a pH-dependent gate, allowing delivery of high concentrations on antibiotics into the host cells for Mycobacterium tuberculosis.

Gerald R. Smith of the Fred Hutchinson Cancer Research Center in the U.S. seeks to identify inhibitors of a bacterial DNA repair enzyme that allows tuberculosis to mutate. Identifying these inhibitors could lead to therapies that kill bacteria and limit drug resistance.

To optimize the effectiveness of current anti-tuberculosis drugs, Boitumelo Semete of the CSIR in South Africa will work with collaborators to develop "sticky nanoparticles" that specifically attach to TB-infected cells. Once taken in by these cells, the nanoparticles will slowly degrade, releasing the anti-TB drugs and killing the bacteria. With this novel drug delivery system, the team aims to improve the bioavailability of the current therapies, with the possibility of shortening the treatment period for TB as well as reduce drug side effects.