The goals of the research at UniCamillus is to combat tuberculosis
Two new strategies to combat the strains of tuberculosis resistant to the cures are the base of the new perspectives for the creation of future drugs by considering that there are many delays on this part. The tuberculosis bacterium, that is transmitted by air, hits 9 million people worldwide and even today kills almost two million per year, 500 in Italy alone.
Nowadays, the WHO is especially concerned about the new strains that are being resistant to the cures: Mdr-Tb (multiresistance) which provides prolonged cures of up to two years and are extremely expensive (2000 dollars against 20 for the first six month cure) and the most dangerous Xdr-Tb which is the super resistant strain and basically incurable. For this, the new research hypotheses appear particularly significant even if many researchers have taken the same line recently.
It deals with an approach that is partly different compared to the current mechanisms of the anti-Tbc drugs because the interruption of the super resistant strains at each type of cure allows for the discovery of new strategies to attack tuberculosis. Some researchers have been focusing on an enzyme called GlgE which is essential for the development of the Tbs bacterium and is a bacterium which 9 times out of 10 is “imprisoned” by our body during our lifetimes but has no consequences for us. Two thirds of the world’s population lives with this bacteria which the immune system is able to control but not kill. Tbs only becomes active in some cases, in particular due to debilitation, poverty, poor hygiene (basically developing countries).
We intend to concentrate on the enzymatic mechanism through which the bacterium of the tuberculosis transform the two glucose molecules (trehalose) into longer sugar molecules known as alfa glucan and which are essentially bricks that maintain the bacteria and its proliferation towards cell division. GlgE is the third of the 4 enzymes involved in the mechanism which leads to the formation of the alfa glucans. It has been observed that by inhibiting the enzyme GlgE, the bacteria have accumulated a toxic molecule, almost a killer poison which damages the Dna of the bacteria and results in death. This has happened in vitro as well as infected mice. The GlgE enzyme has also been shown to be the “perfect target” for a future drug because there are no similar enzymes in man or in the intestinal bacteria.
This line of research appears to be particularly interesting because a second way to kill the tbc bacteria has been witnessed and which concerns the crucial connection between this new way and the synthesis of the alfa glucans and another well-recognized way. It has already been proven that this action doesn’t bring about the death of the bacteria when we eliminate one of the enzymes of the first process which leads to the formation of the alfa glucans; at the same time, making the enzyme inactive (called Rv3032) in the second way, the synthesis of the alfa glucan doesn’t bring about the death of the bacterium. However the process becomes lethal when we make both enzymes inactive: separately the single inactive enzymes don’t bring about consequences and only become killers if they act contemporarily. In fact, the tuberculosis bacterium needs to summarize the alfa glucans but, from the bacterium point of view, it is unthinkable to contemporarily eliminate the two ways which leads to the summaries of the alfa glucans. Either one or the other guarantees the survival. If however we were able to create a drug that could act against both the GlgE and the Rv3032, the combination would be extremely potent. One therapy is cutting the food to the bacterium which would probably take away any possible survival of the bacteria resistant to the drug. Furthermore, another treatment would also be used for leprosy which is an illness linked to another similar bacterium, the mycobacterium of tuberculosis. A clinical verification only seems to be a question of time and UniCamillus is proposing to activate a department ad hoc that develops this research.