Cellular, molecular and functional characterization of quiescence in Leishmania donovani, the etiological agent of visceral leishmaniasis

Quiescence is a survival strategy adopted by several pathogens in
response to prolonged periods of stress, such as drug treatment or
host’s immune response. Quiescent organisms have an overall
downregulated metabolism and they replicate slowly or not at all.
Quiescence of pathogens has major health implications, as it renders
them less susceptible to chemotherapy and allows them to survive
for years unnoticed in the host organism and be the source of
relapses. Quiescence is most extensively studied in bacteria, but
recent reports described this phenomenon in several protozoan
parasites. Leishmania are unicellular eukaryotic parasites causing
leishmaniasis, a neglected tropical disease: the most severe form of
the disease, visceral leishmaniasis, is caused by L. donovani and is
lethal if left untreated. It shows several (sub-)clinical features where
quiescence could play a major role, complicating clinical
management and jeopardizing elimination programs. Studying the
biology of quiescence in L.donovani is thus of utmost importance.
Within a field where a lot is yet to be discovered, we aim to
characterize -in vitro- quiescence in L. donovani, in order to
understand the mechanisms associated with its emergence, its
heterogeneity, its dynamics and its role in parasite adaptation to
stress, including drug treatment. Major findings will be validated in
vivo on experimental animals and will provide knowledge and tools
paving the way for future clinical studies.