Unravelling phenotypic and molecular traits of quiescent populations of Leishmania under drug pressure

Under exposure to stress like drugs, some microorganisms can enter
in quiescence. This is a slow or no-proliferative stage characterized
by a deep down-regulation at metabolic level. Under conditions of
quiescence, a portion of the cell population may survive to the drug,
without developing drug resistance (also called drug indifference).
When the drug is removed, these quiescent cells ‘wake-up’, replicate
again and come back to their normal metabolic activity. Although
quiescence has been described mostly in bacteria, this phenotype
can be adopted by several pathogens encompassing prokaryotes,
protists and fungus. In Leishmania, a unicellular protozoan parasite
causing a major infectious disease, quiescence has been only
recently discovered. Implication of it on drug indifference is unknown,
but could explain the frequent occurrence of treatment failure in the
absence of drug resistance. We hypothesize that quiescent
population of Leishmania can be indifferent to drugs and plan to i)
characterize this phenotype at proteomic and metabolomic level and
ii) identify the genes driving the maintenance of this stage. The
model resulting from this project will be highly relevant among others
for the screening of new drugs active against quiescent forms.