title: Comprehensive proteome analysis of Mycobacterium ulcerans and quantitative comparison of mycolactone biosynthesis.
abstract: Mycobacterium ulcerans is the causative agent of Buruli ulcer, a rapidly emerging human disease in which mycolactone, a cytotoxic and immunosuppressive macrocyclic polyketide, is responsible for massive skin destruction. The genome sequencing of M. ulcerans has recently been accomplished (http://genolist.pasteur.fr/BuruList/) enabling the first proteome study of this important human pathogen. Here, we present a comprehensive proteome analysis of different subcellular fractions and culture supernatant of in vitro grown M. ulcerans. By a combination of gel-based and gel-free techniques for protein and peptide separation with subsequent analysis by MS, we identified 1074 different proteins, corresponding to 25% of the protein-coding DNA sequence. Interestingly, new information was obtained about central metabolism and lipid biosynthesis, and as many as 192 conserved hypothetical proteins were found. Comparative analysis of the wild-type strain and an isogenic mycolactone-deficient mutant, by 2-DE and iTRAQ labeling of the cytoplasmic fraction, revealed differences in the expression profiles of proteins involved in lipid metabolism and information pathways, as well as stress responses.
authors.affiliation: Plate-Forme de Protéomique, Institut Pasteur, Paris, France.
authors.forename: Petra
authors.initials: P
authors.lastname: Tafelmeyer
authors.forename: Christine
authors.initials: C
authors.lastname: Laurent
authors.forename: Pascal
authors.initials: P
authors.lastname: Lenormand
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Rousselle
authors.forename: Laurent
authors.initials: L
authors.lastname: Marsollier
authors.forename: Gilles
authors.initials: G
authors.lastname: Reysset
authors.forename: Runxuan
authors.initials: R
authors.lastname: Zhang
authors.forename: Albert
authors.initials: A
authors.lastname: Sickmann
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Stinear
authors.forename: Abdelkader
authors.initials: A
authors.lastname: Namane
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
mesh_terms: D001426:Bacterial Proteins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000096:biosynthesis*; D015180:Electrophoresis, Gel, Two-Dimensional; D018942:Macrolides; D019911:Mycobacterium ulcerans / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D018942:Macrolides; D020543:Proteome; C117218:mycolactone