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!
Brought to light – chromobodies reveal changes in endogenous protein concentration in living cells
21.09.2018 | NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen
A one-way street for salt
21.09.2018 | Julius-Maximilians-Universität Würzburg
The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.
This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...
Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.
"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...
A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...
21.09.2018 | Event News
03.09.2018 | Event News
27.08.2018 | Event News
21.09.2018 | Physics and Astronomy
21.09.2018 | Life Sciences
21.09.2018 | Event News