Group Leader CNRS, CR
The female germline of Brugia malayi, a filarial nematode causing human filariasis, is aberrant upon Wolbachia endosymbionts depletion.
A wild-type filarial germline with Wolbachia (-in pink, top image) and aberrant after Wolbachia depletion (bottom). DNA is in blue and actin in yellow.
Frederic Landmann and his team are exploring the symbiotic relationship between Wolbachia bacteria and their parasitic hosts, the filarial nematodes. These worms cause debilitating diseases, the filariasis, and infect 100 million people. They rely on intracellular Wolbachia endosymbionts to produce a progeny and to survive. We are investigating the intracellular lifestyle of Wolbachia, and why these endosymbionts are vital for the worms, since they offer a way to cure the disease being therapeutical targets.
Our research focuses on understanding the symbiosis between Wolbachia and parasitic filarial nematodes responsible for human filariasis affecting 100 million people. Filarial nematodes become sterile and die within a few months when the Wolbachia are depleted, while conventional treatments only sterilize these worms which live for more than ten years. This mutualist symbiosis makes Wolbachia a therapeutic target for fighting human and animal filariasis. However, the symbiosis mechanisms established between Wolbachia and the filariae remain poorly described. This is due to two major limitations: Wolbachia, obligate intracellular alpha-proteobacteria are genetically non-tractable, a major obstacle for the research community. In addition, the lack of cell biology tools has so far prevented exploration of the biology of the parasitic nematode, highlighting the need to bridge the gap between classical parasitology of filarial nematodes and cell biology of experimental models such as C. elegans. For these reasons, most of the cellular biology of Wolbachia-host interactions that we know of derives from studies carried out in Drosophila, a natural host of these endosymbionts.
I have developed new gene silencing (RNAi) and immunofluorescence techniques adapted to these large worms which were until then only observed in cross sections.
I described the transmission patterns of Wolbachia in the somatic and germline lines during the development of the worm. I have shown that Wolbachia integrate polarity information to segregate asymmetrically in the embryo, and that an ovarian tropism by extracellular migration is essential to ensure the transmission of endosymbionotic bacteria to the offspring of the parasitic worm. I have demonstrated that the elimination of Wolbachia leads to a major apoptosis in the embryos, cause of the induced sterility.
I have been able to demonstrate with the members of my team that the loss of Wolbachia also affects the oogenesis of the filarial parasite and particularly the behavior of germline stem cells. The reserve fraction of these cells loses its quiescence and their spatial organization becomes chaotic. This observation opens up many questions about the roles of the Wolbachia endosymbionts in this mutualism, which constitute the heart of our research activity.
PhD : 2005 Université Louis Pasteur, Strasbourg, IGBMC, with Dr Michel Labouesse.
Postdoc: 2005-2013 , UCSC, Santa Cruz, CA, USA, with Prof. William Sullivan
1st group leader position:
2013, CNRS, CRBM, Montpellier
2019, Microbiol Spectr