title: Linking in vitro and in vivo survival of clinical Leishmania donovani strains.
abstract: BACKGROUND
  Leishmania donovani is an intracellular protozoan parasite that causes a lethal systemic disease, visceral leishmaniasis (VL), and is transmitted between mammalian hosts by phlebotomine sandflies. Leishmania expertly survives in these 'hostile' environments with a unique redox system protecting against oxidative damage, and host manipulation skills suppressing oxidative outbursts of the mammalian host. Treating patients imposes an additional stress on the parasite and sodium stibogluconate (SSG) was used for over 70 years in the Indian subcontinent.
  
  
  RESULTS
  We evaluated whether the survival capacity of clinical L. donovani isolates varies significantly at different stages of their life cycle by comparing proliferation, oxidative stress tolerance and infection capacity of 3 Nepalese L. donovani strains in several in vitro and in vivo models. In general, the two strains that were resistant to SSG, a stress encountered in patients, attained stationary phase at a higher parasite density, contained a higher amount of metacyclic parasites and had a greater capacity to cause in vivo infection in mice compared to the SSG-sensitive strain.
  
  
  CONCLUSIONS
  The 2 SSG-resistant strains had superior survival skills as promastigotes and as amastigotes compared to the SSG-sensitive strain. These results could indicate that Leishmania parasites adapting successfully to antimonial drug pressure acquire an overall increased fitness, which stands in contrast to what is found for other organisms, where drug resistance is usually linked to a fitness cost. Further validation experiments are under way to verify this hypothesis.
authors.affiliation: Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Manu
authors.initials: M
authors.lastname: Vanaerschot
authors.forename: Ilse
authors.initials: I
authors.lastname: Maes
authors.forename: Meriem
authors.initials: M
authors.lastname: Ouakad
authors.forename: Vanessa
authors.initials: V
authors.lastname: Adaui
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.forename: Simonne
authors.initials: S
authors.lastname: De Doncker
authors.forename: Suman
authors.initials: S
authors.lastname: Rijal
authors.forename: François
authors.initials: F
authors.lastname: Chappuis
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Dujardin
authors.forename: Saskia
authors.initials: S
authors.lastname: Decuypere
mesh_terms: D000818:Animals; D000967:Antimony Sodium Gluconate / Q000494:pharmacology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007893:Leishmania donovani / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology*; D007898:Leishmaniasis, Visceral; D008670:Metals / Q000494:pharmacology; D051379:Mice; D009603:Nitroso Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D013696:Temperature
chemical_list: D008670:Metals; D009603:Nitroso Compounds; D000967:Antimony Sodium Gluconate
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