Presenter: 1.Prof. Eric Rubin, 2.Babak Javid, 3.Ka-Wing Wong

University:

1.Harvard University

2.Tsinghua University

3.Howard Hughes Medical Institute; Albert Einstein College of Medicine

Time: 9:00-12:00, December 2, 2011

Venue: A203, Institute of Microbiology, Chinese Academy of Sciences

Abstract:

1. Abnormal proteins are a constant source of cellular stress in all cells.  These can arise from errors in translation or postranslational damage.  Bacteria have evolved many mechanisms to refold or eliminate abnormal proteins. These seem to be particularly critical in mycobacteria. Here I will discuss the role of the Clp protein degradation system and how it can be exploited to help understand antibiotics and their targets.--- Eric Rubin

2. All cellular functions rely on an adequate fidelity of protein translation and as such, multiple mechanisms exist to ensure accurate translation. Recent evidence has emerged, however, that errors in protein translation (mistranslation) occur at much higher frequencies than previously appreciated. It is not clear, however, whether cells merely tolerate translational errors or if they have evolved to take advantage of mistranslation to adapt to stressful environments. Here, we show that mycobacteria engineered to misincorporate glutamate and aspartate have thousands-fold more tolerance to the antibiotic rifampicin. Furthermore, substantial rates of mistranslation occur physiologically in response to environmental stress. We propose that specific amino acid mistranslation may be a source for adaptive proteomic diversity for microbial populations.---- Babak Javid

3. Necrotic death in macrophages is a primary virulence determinant of Mycobacterium tuberculosis. The ESX-1 secretion system and its substrate ESAT-6 are required for M. tuberculosis to induce necrosis, but host factors that mediate the ESAT-6-promoted necrosis remain unknown. Here I report that ESAT-6-promoted necrotic death in THP-1 human macrophages is dependent on the NLRP3 inflammasome, as shown by RNA interference and pharmacological inhibitions.--- Ka-Wing Wong