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Perilipin lipid tuberculosis

Jaiyanth Daniel, Nidhi Kapoor, Tatiana Sirakova, Rajesh Sinha, Pappachan Kolattukudy
Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one-third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet homeostasis but no such protein has been identified in Mtb. We identified an Mtb protein (PPE15) that showed weak amino acid sequence identities with mammalian perilipin-1 and was upregulated in Mtb dormancy. We generated a ppe15 gene-disrupted mutant of Mtb and examined its ability to metabolically incorporate radiolabeled oleic acid into TAG, accumulate lipid droplets containing TAG and develop phenotypic tolerance to rifampicin in two in vitro models of dormancy including a three-dimensional human granuloma model...
September 2016: Molecular Microbiology
Rachel J Church, Hong Wu, Merrie Mosedale, Susan J Sumner, Wimal Pathmasiri, Catherine L Kurtz, Mathew T Pletcher, John S Eaddy, Karamjeet Pandher, Monica Singer, Ameesha Batheja, Paul B Watkins, Karissa Adkins, Alison H Harrill
Isoniazid (INH), the mainstay therapeutic for tuberculosis infection, has been associated with rare but serious hepatotoxicity in the clinic. However, the mechanisms underlying inter-individual variability in the response to this drug have remained elusive. A genetically diverse mouse population model in combination with a systems biology approach was utilized to identify transcriptional changes, INH-responsive metabolites, and gene variants that contribute to the liver response in genetically sensitive individuals...
August 1, 2014: Toxicological Sciences: An Official Journal of the Society of Toxicology
Patrick M McDonough, Ramses M Agustin, Randall S Ingermanson, Patricia A Loy, Benjamin M Buehrer, James B Nicoll, Natalie L Prigozhina, Ivana Mikic, Jeffrey H Price
Intracellular lipid droplets are associated with a myriad of afflictions including obesity, fatty liver disease, coronary artery disease, and infectious diseases (eg, HCV and tuberculosis). To develop high-content analysis (HCA) techniques to analyze lipid droplets and associated proteins, primary human preadipocytes were plated in 96-well dishes in the presence of rosiglitazone (rosi), a PPAR-(c) agonist that promotes adipogenesis. The cells were then labeled for nuclei, lipid droplets, and proteins such as perilipin, protein kinase C (PKC), and hormone-sensitive lipase (HSL)...
October 2009: Assay and Drug Development Technologies
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