title: Molecular analysis of the Mycobacterium tuberculosis lux-like mel2 operon.
abstract: Using a high throughput genetic strategy, designated Random Inducible Controlled Expression (RICE), we identified the six gene mel2 locus in Mtb and M. marinum. Interestingly, three of the genes present in mel2 have similarities to bioluminescence genes. Similar to other bacterial bioluminescence systems, mel2 facilitates detoxification of reactive oxygen species (ROS). Through the use of thin layer chromatography (TLC) we demonstrate enhanced production of the cell wall virulence lipid, pthiocerol dimycoserosate (PDIM), in a Mtb mel2 mutant relative to the wild type strain in the presence of both H2O2 and diamide oxidative stresses. Furthermore, propionate toxicity assays revealed increased accumulation of triacylglycerol (TAG) in the mel2 mutant relative to wild type. These observations provide the first evidence that mel2 plays a critical role in Mtb lipid biosynthesis.
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Center for Airborne Pathogens Research and Imaging, Medical Research & Education Building, 8447 State Hwy 47, Bryan, TX 77807, USA.
authors.forename: Harish K
authors.initials: HK
authors.lastname: Janagama
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Center for Airborne Pathogens Research and Imaging, Medical Research & Education Building, 8447 State Hwy 47, Bryan, TX 77807, USA.
authors.forename: Sambou
authors.initials: S
authors.lastname: Tounkang
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Center for Airborne Pathogens Research and Imaging, Medical Research & Education Building, 8447 State Hwy 47, Bryan, TX 77807, USA.
authors.forename: Suat L G
authors.initials: SL
authors.lastname: Cirillo
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583-0905, USA.
authors.forename: Denise K
authors.initials: DK
authors.lastname: Zinniel
authors.affiliation: School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583-0905, USA.
authors.forename: Raúl G
authors.initials: RG
authors.lastname: Barletta
authors.affiliation: Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Center for Airborne Pathogens Research and Imaging, Medical Research & Education Building, 8447 State Hwy 47, Bryan, TX 77807, USA. Electronic address: jdcirillo@medicine.tamhsc.edu.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Cirillo
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002473:Cell Wall / Q000378:metabolism*; D002855:Chromatography, Thin Layer; D005816:Genetic Complementation Test; D006801:Humans; D008055:Lipids / Q000096:biosynthesis*; D008164:Luminescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009165:Mycobacterium Infections, Nontuberculous / Q000235:genetics / Q000382:microbiology; D019910:Mycobacterium marinum / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D009876:Operon; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D008055:Lipids; D008164:Luminescent Proteins; D017382:Reactive Oxygen Species
keywords: Bioluminescence; Lipids; Mycobacteria; PDIM; Redox stress; TAG; mel2