title: Use of an adipocyte model to study the transcriptional adaptation of Mycobacterium tuberculosis to store and degrade host fat.
abstract: During its persistence in the infected host, Mycobacterium tuberculosis (Mtb) accumulates host-derived fatty acids in intracytoplasmic lipid inclusions as triacylglycerols which serve primarily as carbon and energy reserves. The Mtb genome codes for more than 15 triacylglycerol synthases, 24 lipase/esterases, and seven cutinase-like proteins. Hence, we looked at the expression of the corresponding genes in intracellular bacilli persisting amidst the host triacylglycerols. We used the Mtb infected murine adipocyte model to ensure persistence and transcripts were quantified using real-time reverse transcriptase polymerase chain reaction. Dormancy and glyoxylate metabolism was confirmed by the upregulated expression of dosR and icl, respectively, by intra-adipocyte bacilli compared with in vitro growing bacilli. The study revealed that tgs1, tgs2, Rv3371, and mycolyltransferase Ag85A are the predominant triacylglycerol synthases, while lipF, lipH, lipJ, lipK, lipN, lipV, lipX, lipY, culp5, culp7, and culp6 are the predominant lipases/esterases used by Mtb for the storage and degradation of host-derived fat. Moreover, it was observed that many of these enzymes are used by Mtb during active replication rather than during nonreplicating persistence, indicating their probable function in cell wall synthesis.
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Shivangi
authors.initials: S
authors.lastname: Rastogi
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Agarwal
authors.affiliation: Division of Microbiology, CSIR-Central Drug Research Institute, Lucknow, India. Electronic address: manju@cdri.res.in.
authors.forename: Manju Y
authors.initials: MY
authors.lastname: Krishnan
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D017667:Adipocytes / Q000378:metabolism / Q000382:microbiology*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D006038:Glyoxylates / Q000378:metabolism; D054884:Host-Pathogen Interactions; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; D006038:Glyoxylates; D011494:Protein Kinases; D008049:Lipase; C031150:glyoxylic acid
keywords: Adipocyte; Cutinase-like proteins; Host lipids; Lipase; Triacylglycerol