Totally drug-resistant TB

One of the biggest problems in Tuberculosis (TB) therapy nowadays is that patients have to take antibiotics for up to 9 months. As many patients feel better before this time, they prematurely stop their treatment, leaving pools of the most drug-resistant M. tuberculosis in their lungs. This contributes to the emergence of complete drug resistance in future patients.

In the past few years, strains of drug-resistant Mtb have become prevalent. In fact, resistance is so widespread that it is now being classified as multi-drug resistant (MDR-TB) and extreme-drug resistant (XDR-TB). Two of the world’s most populous countries, India and China, account for more than 50% of the world’s MDR-TB cases.

Recent reports have also confirmed a new Mtb strain that is completely untreatable and has been designated as Totally drug resistance TB (TDR-TB). Indeed, strains of Mtb have even evolved resistance to all major available anti-TB drugs. India (2012) is the third country in which a total drug-resistant form of TB has emerged, following cases documented in Italy in 2007 and Iran in 2009. There is a need for a more readily available treatment that is effective against both sensitive and drug-resistant strains of M. tuberculosis is evident.

Nano reactions

Recently, nanoporous materials have emerged as important and efficient heterogeneous catalysts for organic transformations due to their excellent textural characteristics, including high surface area, large pore volume, uniform pore size distribution, and simplicity in workup recyclability. The pore diameters are chosen to control the access of molecules to the catalytic reaction sites located inside the porous cavities. Only the molecules of specific sizes and chemical properties are selected and guided to the reaction centers, where they are efficiently transformed to the desired products.

What is a PhD worth?

Here is another article  in nature that makes some good points about the worth of a Ph.D.

"The number of science doctorates earned each year grew by nearly 40% between 1998 and 2008, to some 34,000, in countries that are members of the Organisation for Economic Co-operation and Development (OECD). The growth shows no sign of slowing: most countries are building up their higher-education systems because they see educated workers as a key to economic growth. But in much of the world, science Ph.D. graduates may never get a chance to take full advantage of their qualifications"

Ph.D. program used to be for science-loving driven people, and the world wants more innovation from academic science to solve global problems.

Mycobacteria and the great wall

The mycobacterial cell wall is unique, thick waxy, and hydrophobic, ensuring its survival inside human macrophages by resisting oxidative damages. The waxy, highly impermeable nature of the wall provides the required defense mechanism against antibiotic agents and the host organisms. A key component of the cell wall is mycolic acids. Mycolic acid accounts for up to 60% of the organisms' dry weight, which means that most percentage of mycobacteria is a cell wall. A thorough understanding of the influence of polarity on drug penetration into a highly impermeable mycobacterial cell wall will improve permeability.

The permeation ability of a lipophilic molecule is inversely related to the cell wall's fluidity, which decreases as the length of fatty acids in the mycolic acids layer increases. The permeability barrier presented by this cell envelope is also thought to be why many common antibiotics are ineffective against mycobacteria. Lipophilic drugs, such as fluoroquinolones or rifamycins, pass more quickly through the lipid-rich cell wall and thus are more active.

Depending on the library screens towards compounds with a particular physicochemical parameter could be detrimental and decrease the diversity in finding new anti-TB drugs.

Enoyl reductase: One target, Two major Global Threats

Tuberculosis and Malaria are two major global threats; both account for 5 million deaths annually (mostly in developing countries). Despite the worldwide ravages of Tuberculosis and Malaria, chemotherapeutic regimens against these two diseases have remained largely unchanged. There is an urgent need to develop novel, effective, and affordable drugs to treat both diseases because the resistance has developed or is developing to existing therapy. Scientists around the world are seeking new ways to combat the two opportunistic pathogens.

Mycobacterium tuberculosis and Plasmodium Falciparum are causative agents of tuberculosis and malaria, respectively. Both organisms share enzymatic components of the type II fatty acid biosynthetic pathway (FAS-II). Enoyl acyl carrier protein reductase (ENR) is one of the key type II enzymes, has been repeatedly validated as an effective antimicrobial target (e.g., INH, diazoborines, triclosan, and thiolactomycin).

Triclosan, the ENR inhibitor, showed excellent activity against both organisms. Targeting ENR  with a new class of compounds may yield new drugs against these devastating pathogens.