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: Petra Tafelmeyer, Christine Laurent, Pascal Lenormand, Jean-Claude Rousselle, Laurent Marsollier, Gilles Reysset, Runxuan Zhang, Albert Sickmann, Timothy P Stinear, Abdelkader Namane, Stewart T Cole
• Journal: Proteomics (Proteomics) Vol. 8 Issue 15 Pg. 3124-38 (Aug 2008) ISSN: 1615-9861 [Electronic] Germany
• PMID: 18615429 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Proteins
• Bacterial Toxins
• Macrolides
• Proteome
• mycolactone

Topics

• Bacterial Proteins (analysis, genetics, metabolism)
• Bacterial Toxins (biosynthesis)
• Electrophoresis, Gel, Two-Dimensional
• Macrolides
• Mycobacterium ulcerans (genetics, metabolism)
• Proteome (analysis, genetics, metabolism)
• Proteomics (methods)
• Spectrometry, Mass, Electrospray Ionization
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Tandem Mass Spectrometry