Linking in vitro and in vivo survival of clinical Leishmania donovani strains

M Vanaerschot, I Maes, M Ouakad, V Adaui, L Maes, S De Doncker, S Rijal, F Chappuis, JC Dujardin, S Decuypere

    Research output: Contribution to journalA1: Web of Science-article

    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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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
    Original languageEnglish
    JournalPLoS ONE
    Volume5
    Issue number8
    Pages (from-to)e12211
    Number of pages9
    ISSN1932-6203
    DOIs
    Publication statusPublished - 2010

    Keywords

    • B780-tropical-medicine
    • Protozoal diseases
    • Leishmaniasis
    • Visceral
    • Kala azar
    • Leishmania donovani
    • Isolation
    • Survival
    • Life cycle
    • In vitro
    • In vivo
    • Strains
    • Promastigotes
    • Adaptation
    • Fitness inheritance

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