Tuberculosis

Babak Javid of Tsinghua University School of Medicine in China will determine whether drugs that increase the accuracy of protein production in Mycobacterium tuberculosis, which causes TB, can boost the effect of existing TB drugs and thereby shorten the current 6 month treatment period. They hypothesized that resistance to TB drugs is caused in part by the ability of the bacterium to change its proteins by making random errors during their synthesis (known as mistranslation).

Antonio Campos-Neto of The Forsyth Institute in the U.S. along with collaborators Nira Pollock of The Beth Israel Deaconess Medical Center/Harvard Medical School and David Duffy of Quanterix Corporation, seek to validate seven M. tuberculosis proteins found in the urine of tuberculosis patients as biomarkers of active disease. The ultimate goal is to use the most promising markers to develop a non-invasive point-of-care test, which could be similar to a simple home-pregnancy test.

Robert Moritz and colleagues at the Institute for Systems Biology and Seattle Biomed in the U.S. will use ultra-sensitive targeted assay technology to identify, quantify, and validate a library of biomarker candidates specific to both active and latent TB infection. Moritz and his team hope to discover highly specific proteins that could help determine disease status at the point of care and inform appropriate treatment.

Urs Ochsner of SomaLogic, Inc. in the U.S. will lead a team to expand and test a library of SOMAmers (slow off-rate modified aptamers) to identify protein biomarkers that indicate active tuberculosis from a small sample of blood. SOMAmers, which are modified nucleic acid-based protein-binding agents, offer several advantages over the antibodies traditionally used in diagnostic tests including greater stability, lower cost, and no need for refrigeration.

David Alland of the University of Medicine and Dentistry of New Jersey in the U.S., in collaboration with Advantageous Systems (ADS), will develop a method that uses paramagnetic nanoparticles conjugated with capture antibodies to quickly extract M. tuberculosis bacteria from a patient's sputum sample. This simple extraction method can be applied to a broad range of detection technologies, enabling rapid tuberculosis detection.

John Belisle of Colorado State University in the U.S. will assess the feasibility of using small molecules created by the metabolic processes of host or pathogen cells, as well as lipids and fatty acids produced by the TB bacterium, as biomarkers of active disease.

David Anderson of the Macfarlane Burnet Institute in Australia will examine a unique aspect of the host antibody response that may better differentiate current and past tuberculosis infections. If successful, this approach could be readily incorporated in simple, disposable blood test formats that are currently used for diagnosis in resource-poor settings.

Dan Feldheim of the University of Colorado at Boulder in the U.S. and collaborators Bruce Eaton of the University of Colorado and Delphi Chatterjee of Colorado State University propose to develop new modified DNA aptamer affinity reagents for detecting urine biomarkers of M. tuberculosis active disease. These reagents could form the basis of low-cost, low-power diagnostic sensors for use in resource-limited settings.

Karen Dobos of Colorado State University in the U.S., along with Jeff Schorey of the University of Notre Dame and their partners at the University of San Francisco, seek to identify and validate protein signatures on exosomes, which are small vesicles secreted by M. tuberculosis-infected host cells, for use as biomarkers to diagnose TB. These protein signatures seem to be concentrated by exosomes in such a way that they could be used as highly sensitive indicators of disease in diagnostic tests.

James E. Graham, Xiao-­An Fu, Michael H. Nantz, and Richard M. Higashi of the University of Louisville in the U.S. will investigate the use of adsorptive sample plates with chemically reactive coatings to capture, identify, and validate unique volatile organic compounds found in breath samples of TB patients. This approach can establish the basis for a simple point of care test to identify active disease.