A Date with Science: Drug resistance in Leishmania: does it really matter?

This seminar is a part of ITM's 'A Date with Science': a series of academic seminars that take place every last Thursday of the month, live in Antwerp followed by a drink and online.

Programme:

• 3pm – 4pm: Academic seminar in aula Janssens (and online)

• 4pm – 5.30pm: Drink in Karibu at ITM

Speaker: Jean-Claude Dujardin

Title: Drug resistance in Leishmania: does it really matter?

Register:

Please register to attend in person or to follow online

Abstract:
Treatment failure (TF) of infectious diseases can be due to different factors related to the host, the drug, concomitant diseases, and the pathogen itself. From the pathogen's point of view, drug resistance (DR) is generally considered the main factor in TF. Using Leishmania(sis) as a model, we revisit this dogma. In the past, we studied the link between TF and DR as measured by in vitro drug susceptibility assays in different epidemiological settings, parasite species, and drugs. For both antimonials and miltefosine, we found a poor relationship between treatment outcome and drug susceptibility. In light of recent findings, we propose different possible explanations for these discrepancies, which could have a major impact on further research.
In this talk, Jean-Claude Dujardin will address three fundamental questions:

1. Are the right assays used to measure DR?
   To answer this question, advantages and limitations of in vitro susceptibility assays will be discussed and contrasted with the contribution of molecular assays, especially whole-genome sequencing.

2. Are the right parasites studied?
   Drug susceptibility is measured on isolates, and a strong emphasis will be made on the biases associated with the bottleneck of isolation and further selection in culture. Jean-Claude will also show how heterogeneity of parasite populations and an unprecedented level of aneuploidy mosaicism further complicate molecular tracking of DR.

3. Are there other parasite factors that may cause TF without DR?
   The case of co-infection with the endosymbiotic LRV will be briefly addressed, but the major focus will be brought on parasite quiescence, a physiological stage of non-replication and strong metabolic modulation that allows Leishmania to survive stress. Recent findings on the contribution of quiescence to drug tolerance will be presented, and the major conceptual difference with DR will be highlighted. Priority for further research will be discussed.

This presentation stems from an opinion paper that will be published in the April issue of Trends in Parasitology: 'Drug resistance in Leishmania: does it really matter?' by Malgorzata Anna Domagalska, Michael P. Barrett and Jean-Claude Dujardin

Free access until 8/04/23 https://authors.elsevier.com/a/1gc9M5Eb1xFTve

Short Bio:
Jean-Claude Dujardin is a biologist, specialized in (Molecular) Parasitology. He obtained his PhD at the Free University of Brussels (under the supervision of Prof R. Hamers) on the significance of karyotype diversity in Neotropical Leishmania. He is a full Professor at the ITM, where he leads the Molecular Parasitology Unit (MPU). From 2011 to 2021, he headed the department of Biomedical Sciences and also has a 10% Associate Professor affiliation in the dept of Biomedical Sciences, University of Antwerp. Last but not least, he is a lecturer in Parasitology at the University of Namur. He is passionate about Science and the beauty and innovation of life. He is recognized as a multidisciplinary expert on the biology of Leishmania and on parasitological aspects of leishmaniasis, from gene to ecosystems.