Zhong-Yin Zhang, Ph.D., Robert A. Harris Professor and chairman of the Department of Biochemistry and Molecular Biology, and his colleagues revealed the biochemical processes that TB bacteria employ to subvert macrophages – key infection-fighting cells – in this week's online early edition of the Proceedings of the National Academy of Sciences. They also described a compound they have synthesized – I-A09 – that blocked the TB bacterium's activity in laboratory tests.
About one-third of the world's population is infected with TB, a contagious disease that causes nearly 2 million deaths annually, according to the Centers for Disease Control and Prevention. Although medicines to treat TB are available, they must be taken for at least six months to fully eliminate all TB bacteria from the body. People who do not follow the lengthy treatment regimen can become sick and infectious with a more virulent form of the disease that is resistant to standard medicines.
The compound synthesized by the IU group is a proof of concept that a small molecule drug targeted against an essential virulent factor of the TB bacterium can be an effective strategy, Zhang said. If it can be developed into an approved drug, the result could significantly shorten treatment times for TB, he said.
The focus of the research was TB actions inside macrophages, which are infection fighting cells in the body's immune system. Macrophage cells' tools include the production of special proteins called cytokines to attack foreign invaders. Infected macrophages can also initiate a self-destruction mechanism called apoptosis, which signals other immune system cells to mount a defense against the infection.
TB bacteria are able to disable the macrophage defenses by secreting virulent factors into the host. The IU team found that the actions of a particular virulent factor – a protein phosphatase enzyme called mPTPB – blocked both the production of the infection-fighting cytokines, and the macrophage's self-destruct system.
Using combinatorial chemical synthesis and high-throughput screening, the researchers developed the I-A09 compound, which successfully blocked the action of mPTPB. Tests involving live TB bacteria were conducted at the Institute of Tuberculosis Research, University of Illinois at Chicago.
Currently, compound I-A09 is being evaluated in a TB animal model at the Johns Hopkins University School of Public Health. More potent forms of the I-A09 compound are being pursued by the IU team for possible future clinical testing, Dr. Zhang said.
The research was supported by grants from the National Institutes of Health.
Eric Schoch | EurekAlert!
Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München
Second research flight into zero gravity
21.10.2016 | Universität Zürich
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.
In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...
'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.
Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
21.10.2016 | Health and Medicine
21.10.2016 | Information Technology
21.10.2016 | Materials Sciences