Tuberculosis

Todd L. Lowary of the University of Alberta in Canada will develop a library of chemically synthesized glycans, which are antigens found on the cell wall of M. tuberculosis, and prepare a microarray of them to screen for antibodies that signal the presence of active TB.

Kanury Rao of International Centre for Genetic Engineering and Biotechnology in India is testing small molecule inhibitors of host proteins required for M. tuberculosis to survive and replicate within host cells. Identifying and optimizing compounds that target host proteins could lead to new drug therapies for tuberculosis that are effective even against multidrug-resistant bacterial strains. This grant was selected through India's IKP Knowledge Park and their IKP-GCE program.

Rohit Srivastava and Aravind Kumar of the Indian Institute of Technology, Bombay in India will develop a microneedle-based drug delivery system for the treatment of tuberculosis (TB). Current treatment involves frequent administration of combinations of toxic drugs, which often leads to non-compliance necessitating further complex treatments.

Gerard Cangelosi and colleagues at the UW Foundation in the U.S. will develop an oral swabbing method as a lower-cost safe and simple way to diagnose tuberculosis. Tuberculosis is a major global health threat and prompt diagnosis and treatment are critical for reducing spread. Currently a diagnosis is made by testing sputum from deep in the lungs produced by coughing. This can be difficult to collect and produce particularly for children and hazardous for health care workers.

Rakesh Jain of Massachusetts General Hospital in the U.S. will develop a new treatment strategy for tuberculosis to boost the activity of existing anti-tuberculosis drugs. Tuberculosis is one of the most infectious diseases in the world. Current treatments are lengthy poorly tolerated and do not eradicate latent infections which are found in around one third of the general population and contribute to drug resistance. During latent infection the tuberculosis bacteria are dormant and reside in small inflammatory areas in the lungs known as granulomas.

Carl Nathan, Julien Vaubourgeix and Gang Lin of Weill Cornell Medical College will test their hypothesis that tuberculosis is able to exit latency by distributing damaged proteins to a senescent cell lineage, while more functional proteins are diverted to a lineage with full replication potential. Regulating this post-latency cell division could be the target of new drugs. This project's Phase I research demonstrated that M. tuberculosis accumulates irreversibly oxidized proteins when its replication is blocked. These proteins form small aggregates that fuse into larger ones.

Robert Abramovitch of Michigan State University in the U.S. will use their high-throughput drug discovery platform to identify new drugs for treating chronic tuberculosis and for potentially shortening the current treatment time of six to nine months. Their platform exploits a genetic region known as the DosR regulon thought to underlie the behavior of the causative bacteria in humans under low oxygen conditions, when they become dormant and thereby resistant to current drugs.

Hossam Haick of Technion - Israel Institute of Technology in Israel is developing a sensing plaster that can be stuck on the chest to detect volatile biomarkers emitted through the skin for self-diagnosis of tuberculosis even at early stages. The presence of tuberculosis will be signaled by colored LEDs. In Phase I, they evaluated different materials and selected non-toxic nanomaterial-based sensors. They also performed a study of healthy people and tuberculosis patients and identified several candidate volatile compounds that could be detected by the sensors.

Kyu Rhee of Weill Cornell Medical College in the U.S. will test the theory that the tuberculosis (TB) bacterium uses protein-based structures termed metabolosomes to enter into, maintain, and exit from latency or non-replication. Understanding how metabolosomes work will aid in development of drugs that target TB. This project's Phase I research demonstrated that latent or non-replicating M. tuberculosis undergo a metabolic remodeling that is accompanied by the reversible formation of enzyme-based metabolosomes.