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© Research
Event

Video Seminar – Isabelle Louradour -“Deciphering the mechanisms of Leishmania sexual reproduction and interaction with their sand fly vectors”

Scientific Fields
Diseases
Organisms
Applications
Technique
Date
18
Feb 2021
Time
14:00:00
Institut Pasteur, Rue du Docteur Roux, Paris, France
Address
Room: Teams Meeting
Location
2021-02-18 14:00:00 2021-02-18 15:00:00 Europe/Paris Video Seminar – Isabelle Louradour -“Deciphering the mechanisms of Leishmania sexual reproduction and interaction with their sand fly vectors” Isabelle Louradour Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health-Maryland, USA Seminar via MS Teams Link : Cliquez ici pour participer à la réunion “Deciphering the mechanisms […] Institut Pasteur, Rue du Docteur Roux, Paris, France Gérald Spaeth gerald.spaeth@pasteur.fr

About

Isabelle Louradour
Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases,
National Institutes of Health-Maryland, USA

Seminar via MS Teams
Link :
Cliquez ici pour participer à la réunion

“Deciphering the mechanisms of Leishmania sexual reproduction
and interaction with their sand fly vectors”

Abstract : By transmitting pathogens causing important human mortality and morbidity, vector insects are a major public health threat. Phlebotomine sand flies are the vectors of Leishmania parasites, causing a wide spectrum of diseases associated with devastating immune-pathologies. For many arthropod vectors, the gut microbiota negatively impact their vector competence, i.e. their ability to carry and transmit pathogens. Antibiotic treatment of colonized Phlebotomus duboscqi sand flies resulted on the contrary in flies that were refractory to the development of transmissible Leishmania major infections. We showed that the antibiotic induced dysbiosis resulted in an inability of the parasite to survive and to colonize the anterior midgut with infective, metacyclic stage promastigotes parasites. Our data suggest that the positive effect of the gut microbiota on vector competence results from the utilization of sucrose by the bacteria inhabiting the sand fly gut, creating the appropriate osmotic conditions required for the survival and differentiation of infective stage promastigotes in vivo (Louradour et al., Cellular Microbio., 2017). In other vector insects, vector competence is also strongly influenced by the insect immune response. We adapted the CRISPR/Cas9 technology to the Phlebotomus papatasi sand fly, targeting the sand fly immune deficiency (IMD) pathway, well described as crucial for the control of immune response in other insects, in order to decipher its contribution to sand fly vector competence for Leishmania parasites. We were able to generate transmissible null mutant alleles for relish, the only transcription factor of the IMD pathway. In addition to the expected higher level and susceptibility to bacteria, the mutant flies presented higher loads of parasites when infected with Leishmania major, showing that the sand fly immune response negatively impacts its vector competence for this pathogen. This study was the first example of successful targeted mutagenesis in sand flies, via adaptation of the CRISPR/Cas9 editing technique (Louradour et al., mBio 2019).

Finally, in addition to their clonal reproduction inside the sand fly digestive tract, Leishmania parasites can engage in a cryptic sexual cycle resulting in hybrid progeny. Sexual mating is believed to be a major source of Leishmania genetic diversity, which drives changes in differentiation capacities, tissue tropisms, virulence and drug resistance, but the mechansims of Leishmania sexual reproduction are poorly understood. Experimental generation of hybrids was until recently confined to parasites growing in the sand fly gut, strongly limiting the possibilities of investigation. We recently developed a protocol enabling the reproducible generation of Leishmania hybrids in vitro (Louradour et al., Cell Reports 2020). Analysis of SNPs marker inheritance and whole-genome sequencing data indicate that the progeny clones are full genomic hybrids. The demonstration that mating-competent forms arise in culture should facilitate experimental study of the mating biology of Leishmania and the generation of large numbers of recombinant parasites for positional cloning of genes important for parasites to engage in and successfully perform sexual reproduction.

Contact : Gerald Spaeth : gerald.spaeth@pasteur.fr

Location

Room: Teams Meeting
Address: Institut Pasteur, Rue du Docteur Roux, Paris, France