DISCOVERY OF NOVEL DRUG-RESISTANCE GENES INVOLVED IN CANINE LEISHMANIASIS TREATMENT FAILURE
NSERC Discovery Grant RGPIN-2017-04480 awarded to CFP
In the absence of new drugs introduced in recent years, current CanL antileishmanials are restricted to only two drugs; old-fashioned antimonial derivatives and antitumor-drug miltefosine. While it is true they are still effective against sensitive Leishmania populations with which they have never been in contact, their massive use during the last years coupled with the high ability of these parasites to adapt and survive external stress (including drug pressure), has triggered the rapid emergence and spread of highly resistant populations that are easily transmitted from animals to humans, and vice versa. An additional problem is that current antileishmanials have neither well-defined mechanisms of action nor mechanisms of resistance. The here-proposed Research Program aims to discover and investigate novel molecular characters responsible for the development of drug resistance in Leishmania.
Canine leishmaniosis (CanL) is a parasite-borne disease mainly caused by Leishmania infantum. Life-threatening L. infantum infects domestic and wild dogs that subsequently develop different clinical presentations ranging from mild presentation to fatal disease. Furthermore, these infected dogs act as a major reservoir and foci of transmission of resistant Leishmania strains to humans. This dangerous zoonotic disease is increasingly affecting countries where it was previously unknown or had been eradicated for a long time. Traditionally, CanL threatened canine species in Europe and South America. However, alarming evidence points to the introduction of this fatal zoonotic disease into the canine populations of Canada and the United States.