- Stringent response pathways involving inorganic polyphosphate (PolyP) play an essential role in bacterial stress adaptation and virulence. The intracellular levels of PolyP are modulated by the activities of polyphosphate kinase-1 (PPK1), polyphosphate kinase-2 (PPK2), and exopolyphosphatases (PPXs). The genome of Mycobacterium tuberculosis encodes two functional PPXs, and simultaneous deletion of ppx1 and ppx2 results in a defect in biofilm formation. We demonstrate here that these PPXs cumulatively contribute to the ability of M.
- I was recently awarded the Alice and C. C. Wang Award in Molecular Parasitology for my contributions to antimalarial drug development, including laying the groundbreaking work that has led to two new molecular methods for curing malaria. This award means a great deal to me because I have spent much of my scientific career feeling like an imposter—one with the wrong sort of background and poor credentials. I am grateful for the recognition, and I am beginning to recognize that having an atypical background can be an advantage because it gives you a different perspective on a challenge.
- Mycobacterium tuberculosis is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. M. tuberculosis 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. The M. tuberculosis genome encodes 23 such ESAT-6 family proteins.
- Hepatitis C virus (HCV) relies on host lipids and lipid droplets for replication and morphogenesis. The accumulation of lipid droplets in infected hepatocytes manifests as hepatosteatosis, a common pathology observed in chronic hepatitis C patients. One way by which HCV promotes the accumulation of intracellular lipids is through enhancing de novo lipogenesis by activating the sterol regulatory element-binding proteins (SREBPs). In general, activation of SREBPs occurs during cholesterol depletion.
- Background: Decades of observations strengthened the idea that trehalose is a chemical chaperone.Results: A catalytically inactive variant of the trehalose-6P synthase (Tps1) maintains cell survival and energy homeostasis under stress exposure.Conclusion: The Tps1 protein itself, not trehalose, is crucial for cell integrity.Significance: This work provides unbiased evidence for an alternative function of Tps1, a new “moonlighting” protein.