We know about the drug resistant tuberculosis and the havoc its causing, so there is an urgent need to develop new drugs that can be useful. (have covered some articles on drug development for drug resistant TB in my earlier blogs). Many groups have tried to explain the resistance, but now researchers from Indiana University School of Medicine have identified a mechanism used by the tuberculosis bacterium to evade the body's immune system and have identified a compound that blocks the bacterium's ability to survive in the host, which could lead to new drugs to treat tuberculosis.
The focus of the research was TB actions inside macrophages (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.
As for as my knowledge goes, phosphatases (VE-PTP, Cdc25A, PTP1b, VHR, Shp-2, MptpA und MptpB) the key regulators of various life processes are being studied for the diverse activities. The following is the brief summary ;
a). VE-TPT inhibition is very promising in the development of antiangiogenesis inhibitors in cancer therapy.
b). Cdc25A influences cell cycle regulation and may also be a target of interest in cancer therapy.
c). The phosphatase MptpB, from Mycobacterium tuberculosis, influences the host's immune
reaction in a tuberculosis infection.
d) VHR dephosphorylates MAP kinases in the activation loop THX, which plays an important role in signal
transduction processes.
e) Inhibiting MptpB and Shp-2 opens up new directions in the search for antibiotics and
f) The Ptp1B enzyme plays an important role in developing a medicine against type 2 diabetes and the
metabolic syndrome.
Though many researchers tried to study the mechanism of action by which the tuberculosis bacterium is getting resistance, this group has come up with a drug and this is of great significance in my opinion.
Using combinatorial chemical synthesis and high-throughput screening, (HTS) 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.
As per the claim by the lead researcher, Dr. Zhong-Yin Zhang, 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. Hope the team will come up with a solution to this problem in the days to come...
Ref : http://www.medicine.indiana.edu/news_releases/viewRelease.php4?art=1232
