title: Changes in metabolic phenotypes of Plasmodium falciparum in vitro cultures during gametocyte development.
abstract: BACKGROUND
  Gametocytes are the Plasmodium life stage that is solely responsible for malaria transmission. Despite their important role in perpetuating malaria, gametocyte differentiation and development is poorly understood.
  
  
  METHODS
  To shed light on the biochemical changes that occur during asexual and gametocyte development, metabolic characterization of media from in vitro intra-erythrocytic Plasmodium falciparum cultures was performed throughout gametocyte development by applying 1H nuclear magnetic spectroscopy, and using sham erythrocyte cultures as controls. Spectral differences between parasite and sham cultures were assessed via principal component analyses and partial-least squares analyses, and univariate statistical methods.
  
  
  RESULTS
  Clear parasite-associated changes in metabolism were observed throughout the culture period, revealing differences between asexual parasites and gametocyte stages. With culture progression and development of gametocytes, parasitic release of the glycolytic end products lactate, pyruvate, alanine, and glycerol, were found to be dramatically reduced whilst acetate release was greatly increased. Also, uptake of lipid moieties CH(2), CH(3), and CH = CH-CH(2)-CH(2) increased throughout gametocyte development, peaking with maturity.
  
  
  CONCLUSIONS
  This study uniquely presents an initial characterization of the metabolic exchange between parasite and culture medium during in vitro P. falciparum gametocyte culture. Results suggest that energy metabolism and lipid utilization between the asexual stages and gametocytes is different. This study provides new insights for gametocyte-specific nutritional requirements to aid future optimization and standardization of in vitro gametocyte cultivation, and highlights areas of novel gametocyte cell biology that deserve to be studied in greater detail and may yield new targets for transmission-blocking drugs.
authors.forename: Sabrina D
authors.initials: SD
authors.lastname: Lamour
authors.forename: Ursula
authors.initials: U
authors.lastname: Straschil
authors.forename: Jasmina
authors.initials: J
authors.lastname: Saric
authors.affiliation: Department of Life Sciences, Imperial College London, London SW7 2AZ, UK. michael.delves@imperial.ac.uk.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Delves
mesh_terms: D003470:Culture Media / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008660:Metabolism; D010641:Phenotype; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D003470:Culture Media