title: New insights into the survival mechanisms of rifampicin-resistant Mycobacterium tuberculosis.
abstract: OBJECTIVE
  Rifampicin is considered the most important antibiotic for treating TB, but unfortunately Mycobacterium tuberculosis is rapidly developing resistance to this drug. Despite the fervent research efforts to date, TB is still a major global problem, and hence new approaches are necessary to better characterize this disease, especially the mechanisms relating to drug resistance.
  
  
  METHODS
  Using a two-dimensional GC-coupled time-of-flight MS metabolomics approach, the most important metabolite markers characterizing rifampicin-resistant M. tuberculosis were identified.
  
  
  RESULTS
  The metabolite markers identified indicate instability in rifampicin-resistant M. tuberculosis mRNA, induced by the rpoB mutation. This results in a total depletion of aconitic acid, due to a shift in aconitase functionality towards mRNA binding and stability, and away from energy production and growth, and a subsequent increased dependency on alternative energy sources, fatty acids in particular. A number of other metabolic changes were observed, confirming an additional survival response for maintaining/remodelling the cell wall.
  
  
  CONCLUSIONS
  This study shows the value of a metabolomics approach to biological investigations in a quest to better understand disease-causing organisms and their tolerance to existing medications, which would in the future undoubtedly assist in the development of alternative treatment approaches.
authors.affiliation: Human Metabolomics, School for Physical and Chemical Sciences, North-West University, Potchefstroom, Private Bag X6001, Box 269, Postal code 2531, South Africa dutoit.loots@nwu.ac.za.
authors.forename: Du Toit
authors.initials: du T
authors.lastname: Loots
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006801:Humans; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D050296:Microbial Viability / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D012293:Rifampin