Linking in vitro and in vivo survival of clinical Leishmania donovani strains.
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.
Vanaerschot
Manu
M
Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium.
Maes
Ilse
I
Ouakad
Meriem
M
Adaui
Vanessa
V
Maes
Louis
L
De Doncker
Simonne
S
Rijal
Suman
S
Chappuis
François
F
Dujardin
Jean-Claude
JC
Decuypere
Saskia
S
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
D008670:Metals; D009603:Nitroso Compounds; D000967:Antimony Sodium Gluconate
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