Recombinant M. tuberculosis 38kDa (PstS1) antigen [His]

Nanoparticles-based drug delivery is at the forefront in the field of pharmaceutical and medicinal research to eradicate or alleviate the associated impediments, such as prolonged treatment time, high doses, toxicity and resistance problem of anti-tuberculosis drugs for the treatment of age-old tuberculosis disease. Herein, the firstline anti-tuberculosis drugs were loaded into the biodegradable starch nanocrystals and native starch to improve the therapeutic profile addressing the existing issues related to conventional drugs. The loading performance of anti-tuberculosis drugs with starch nanocrystals and native starch was found in the range of 65-95%. According to the release study, the native starch was not appropriate, however, the starch nanocrystals demonstrated sustained release drug delivery for isoniazid and pyrazinamide ranging from 50 to 93% for 24 h; the burst release for streptomycin was reported at pH 2 in 6.5 h while only 14% rifampicin was released at pH 8 buffer. An anti-mycobacterium analysis of strain H37Rv showed that minimum inhibition concentration of starch nanocrystals loaded with isoniazid and pyrazinamide (0.033 mu g/mL and 1.25 mu g/mL, respectively) were more effective than the parent isoniazid (0.2 mu g/mL) and pyrazinamide (25.0 mu g/mL) at pH 5.5.

In mycobacteria, phosphatidylinositol (PI) acts as a common lipid anchor for key components of the cell wall, including the glycolipids phosphatidylinositol mannoside, lipomannan, and lipoarabinomannan. Glycolipids in Mycobacterium tuberculosis, the causative agent of tuberculosis, are important virulence factors that modulate the host immune response. The identity-defining step in PI biosynthesis in prokaryotes, unique to mycobacteria and few other bacterial species, is the reaction between cytidine diphosphate-diacylglycerol and inositol-phosphate to yield phosphatidylinositol-phosphate, the immediate precursor to Pl. This reaction is catalyzed by the cytidine diphosphate-alcohol phosphotransferase phosphatidylinositol-phosphate synthase (PIPS), an essential enzyme for mycobacterial viability. Here we present structures of PIPS from Mycobacterium kansasii with and without evidence of donor and acceptor substrate binding obtained using a crystal engineering approach. PIPS from Mycobacterium kansasii is 86% identical to the ortholog from M. tuberculosis and catalytically active. Functional experiments guided by our structural results allowed us to further characterize the molecular determinants of substrate specificity and catalysis in a new mycobacterial species. This work provides a framework to strengthen our understanding of phosphatidylinositol-phosphate biosynthesis in the context of mycobacterial pathogens. (C) 2020 Elsevier Ltd. All rights reserved.