The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD.

Mycobacterium tuberculosis (Mtb) induces necrosis of infected cells to evade immune responses. Recently, we found that Mtb uses the protein CpnT to kill human macrophages by secreting its C-terminal domain, named tuberculosis necrotizing toxin (TNT), which induces necrosis by an unknown mechanism. Here we show that TNT gains access to the cytosol of Mtb-infected macrophages, where it hydrolyzes the essential coenzyme NAD(+). Expression or injection of a noncatalytic TNT mutant showed no cytotoxicity in macrophages or in zebrafish zygotes, respectively, thus demonstrating that the NAD(+) glycohydrolase activity is required for TNT-induced cell death. To prevent self-poisoning, Mtb produces an immunity factor for TNT (IFT) that binds TNT and inhibits its activity. The crystal structure of the TNT-IFT complex revealed a new NAD(+) glycohydrolase fold of TNT, the founding member of a toxin family widespread in pathogenic microorganisms

T. Ramakrishnan (1922–2008)

Tekkepat Ramakrishnan (formerly, Indian Institute of Science (IISc), Bangalore) passed away on 15 February 2008 at Bangalore. He was suffering from Parkinson’s disease for the past few years and the syndrome had reached an advanced state prior to his demise. The cause of his death was pneumonia and the end was peaceful. In the sad demise of Ramakrishnan, the country has lost an excellent scientist with great vision

The terminator saga

The terminator concept and its impending consequences in agriculture have been hitting our daily newspaper headlines. The terminator gene if expressed within a seed, will mark the death of the seed and the target can be cotton, millets, rice, wheat or corn. the expression of the terminator itself can be modulated at will. the apprehension has been whether the engineered terminator gene will eradicate particular species of crop plants by preventing the seeds to germinate. Worse still, what if the trait spreads to nontarget crops? These questions evidently are of great concern to our farmers who have been following the age-old practice of saving a portion of their harvest for sowing the next crop and these seeds do not germinate whereas the seed he procures from the industry behaves normally! I have tried to explain here the scientific principles of the terminator concept and how it can be technically achieved without taking sides for or against

The terminator: Saga continues

In my article entitled "The terminator saga", I had explained the basic principles of regulation of gene expression (based on Jacob-Monod model) and how gene expression can be possibly regulated tissue specifically and development stage specifically

Molecular cloning and expression pattern of a Cubitus interruptus homologue from the mulberry silkworm Bombyx mori

A homologue of the segment polarity gene Cubitus interruptus from Bombyx Mori, (BmCi) has been cloned and characterized. This region harbouring Zn2+ finger motif is highly conserved across species. In B. Mori, BmCi RNA expression was first detected at stage 6 of embryogenesis, which reached maximum levels at stage 21C and was maintained until larval hatching. The segmentally reiterated striped pattern of transcript distribution in stage 21C embryos was in conformity with its predicted segment polarity nature. BmCi was expressed in the fore- and hind-wing discs, ovaries, testes and gut during fifth larval intermolt, reminiscent of its expression domains in Drosophila. Besides, BmCi expression was seen in the. anterior part of the middle silkglands in late embryonic stages, and this pattern was maintained during larval development. The transition from third to fourth and fifth larval intermolts was accompanied by an increase in the transcript levels in the middle silkglands. Our results demonstrate the presence of a novel expression domain for Ci in Bombyx. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved