Mechanisms of symbiosis with Wolbachia

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From nematodes to insects…

Wolbachia are widespread bacteria in nature. They live in symbiosis with an amazing diversity of arthropod species, and are also hosted by parasitic filarial nematodes. These bacteria have the amazing peculiarity of being transmitted by the host female germ line to the offspring, like mitochondria. As Wolbachia can affect the biology of their hosts, which can be disease vectors (for instance, mosquitos or human parasites), they are of utmost biomedical relevance. Filariasis is a highly debilitating vector-borne disease that affects over 120 million people in tropical areas. It is caused by parasitic nematodes that live in mutualism with Wolbachia. Without their symbionts, these worms become sterile and quickly die. Therefore, Wolbachia is a promising drug target. We study the cellular and molecular mechanisms underlying the symbiosis with Wolbachia in nematodes and insects. To this aim, we develop new techniques of observation and investigation, especially for filarial nematodes.

Outstanding questions:
We use a multispecies approach to address key issues:

  1. What are the transmission mechanisms of Wolbachia, within an organism (from the zygote to the adult germline), and within an insect population?
  2. Why are Wolbachia required for the survival and fertility of the filarial species they colonize?
  3. How do Wolbachia subvert the host cell machinery to establish and maintain their intracellular lifestyle?

Models we use:
To address these questions, we use the natural hosts of Wolbachia as experimental models, such as Brugia malayi (the causative agent of elephantiasis) and other filarial nematodes species, as well as the Drosophila fly and the Culex pipens mosquito.

Main publications 

Wolbachia control stem cell behavior and stimulate germline proliferation in filarial nematodes

Vincent Foray*, Mercedes M.Perez-Jiménez*, Nour Fattouh, Frédéric Landmann

Developmental Cell, accepted.

Contact our team

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Frederic Landmann

Members of the team

  • Aurelien DROUARD
    (Research Assistant) +33 (0)4 34 35 95 65
  • Frederic LANDMANN Group Leader
    (CRCN) +33 (0)4 34 35 95 65
  • Kevin TERRETAZ
    (Research Assistant) +33 (0)4 34 35 95 83
    • 2019

      Wolbachia endosymbionts subvert the endoplasmic reticulum to acquire host membranes without triggering ER stress.

      Fattouh N, Cazevieille C, Landmann F.

      PLoS Negl Trop Dis. 13(3):e0007218. Pubmed

    • 2019

      The Wolbachia Endosymbionts.

      Landmann F.

      Microbiol Spectr. 7(2). Pubmed

    • 2018

      Wolbachia Control Stem Cell Behavior and Stimulate Germline Proliferation in Filarial Nematodes.

      Foray V, Pérez-Jiménez MM, Fattouh N, Landmann F.

      Dev Cell. 45(2):198-211. Pubmed

    • 2016

      Non-centrosomal epidermal microtubules act in parallel to LET-502/ROCK to promote C. elegans elongation.

      Quintin S, Wang S, Pontabry J, Bender A, Robin F, Hyenne V, Landmann F, Gally C, Oegema K, Labouesse M.

      Development. 143:160-73. Pubmed

    • 2014

      Drosophila protamine-like Mst35Ba and Mst35Bb are required for proper sperm nuclear morphology but are dispensable for male fertility.

      Tirmarche S, Kimura S, Sapey-Triomphe L, Sullivan W, Landmann F, Loppin B.

      G3 (Bethesda). 4:2241-5. Pubmed

    • 2014

      Co-evolution between an endosymbiont and its nematode host: Wolbachia asymmetric posterior localization and AP polarity establishment.

      Landmann F, Foster JM, Michalski ML, Slatko BE, Sullivan W.

      PLoS Negl Trop Dis. 28:e3096. Pubmed

    • 2014

      Absence of Wolbachia endobacteria in the human parasitic nematode Dracunculus medinensis and two related Dracunculus species infecting wildlife.

      Foster JM, Landmann F, Ford L, Johnston KL, Elsasser SC, Schulte-Hostedde AI, Taylor MJ, Slatko BE.

      Parasit Vectors. 7:140. Pubmed

    • 2013

      Interdomain lateral gene transfer of an essential ferrochelatase gene in human parasitic nematodes.

      Wu B, Novelli J, Jiang D, Dailey HA, Landmann F, Ford L, Taylor MJ, Carlow CK, Kumar S, Foster JM,[...]

      Proc Natl Acad Sci U S A. 110(19):7748-53. Pubmed

    • 2012

      Efficient in vitro RNA interference and immunofluorescence-based phenotype analysis in a human parasitic nematode, Brugia malayi.

      Landmann F, Foster JM, Slatko BE, Sullivan W.

      Parasit Vectors. 5:16. Pubmed

    • 2012

      A cell-based screen reveals that the albendazole metabolite, albendazole sulfone, targets Wolbachia.

      Serbus LR, Landmann F, Bray WM, White PM, Ruybal J, Lokey RS, Debec A, Sullivan W.

      PLoS Pathog. 8(9):e1002922. Pubmed

    • 2012

      A new type F Wolbachia from Splendidofilariinae (Onchocercidae) supports the recent emergence of this supergroup.

      Lefoulon E, Gavotte L, Junker K, Barbuto M, Uni S, Landmann F, Laaksonen S, Saari S, Nikander S, de Souza[...]

      Int J Parasitol. 42(11):1025-36. Pubmed

    • 2012

      Both asymmetric mitotic segregation and cell-to-cell invasion are required for stable germline transmission of Wolbachia in filarial nematodes.

      Landmann F, Bain O, Martin C, Uni S, Taylor MJ, Sullivan W.

      Biol Open. 1(6):536-47. Pubmed

    • 2011

      A tension-induced mechanotransduction pathway promotes epithelial morphogenesis.

      Zhang H, Landmann F, Zahreddine H, Rodriguez D, Koch M, Labouesse M.

      Nature. 471(7336):99-103. Pubmed

    • 2011

      New insights into the evolution of Wolbachia infections in filarial nematodes inferred from a large range of screened species.

      Ferri E, Bain O, Barbuto M, Martin C, Lo N, Uni S, Landmann F, Baccei SG, Guerrero R, de Souza[...]

      PLoS One. 6(6):e20843. Pubmed

    • 2011

      Anti-filarial activity of antibiotic therapy is due to extensive apoptosis after Wolbachia depletion from filarial nematodes.

      Landmann F, Voronin D, Sullivan W, Taylor MJ.

      PLoS Pathog. 7(11):e1002351. Pubmed

    • 2010

      Asymmetric Wolbachia segregation during early Brugia malayi embryogenesis determines its distribution in adult host tissues.

      Landmann F, Foster JM, Slatko B, Sullivan W.

      PLoS Negl Trop Dis. 4(7):e758. Pubmed

    • 2009

      Wolbachia-mediated cytoplasmic incompatibility is associated with impaired histone deposition in the male pronucleus.

      Landmann F, Orsi GA, Loppin B, Sullivan W.

      PLoS Pathog. 5(3):e1000343. Pubmed

    • 2008

      The genetics and cell biology of Wolbachia-host interactions.

      Serbus LR, Casper-Lindley C, Landmann F, Sullivan W.

      Annu Rev Genet. 42:683-707. Pubmed

    Wolbachia and filarial nematodes.

    Filarial parasites cause neglected tropical diseases (filiariases) that affect more than 120 million people. Filiriases are debilitating diseases and include elephantiasis (lymphatic filariasis) and the african river blindness (Onchocerciasis). The Wolbachia endosymbionts are required for proper fertility and survival of adult filarial nematodes. Moreover, they participate in the pathology caused by the filarial nematodes by triggering inflammatory reactions when released from dead larvae and are the cause of blindness in Onchocerciasis. Wolbachia are now a major drug target to fight filarial diseases because the current anti-parasitic treatments do not kill adult worms. This is a serious problem because worms can live more than a decade in their host and the females release hundreds of larvae every day.

    During the embryogenesis of Brugia malayi (one of the causative agents of elephantiasis) Wolbachia segregate asymmetrically to reach a subset of hypodermal precursors. In juvenile adult females, the endosymbionts present in the hypodermis show an ovarian tropism and colonize the germline.
    We are interested in the cellular and molecular characterization of these complex transmission mechanisms.

    Cytoplasmic Incompatibility.

    Fruit fly species and mosquitoes, among many other species of insects, can be natural Wolbachia hosts. In both cases, Wolbachia parasites are not essential for their host survival/fertility, but they manipulate the host reproduction machinery to their own advantage in order to ensure their transmission to the next generation. Indeed, Wolbachia bacteria use a strategy called Cytoplasmic Incompatibility (CI) to spread in a given insect population. CI is a complex process that leads to the death of uninfected progeny resulting from non-infected females fertilized by infected males (a dead end for maternally transmitted bacteria).  Therefore, infected females and their infected progeny end up with a selective advantage.  Specifically, fertilization of non-infected eggs by sperm from a Wolbachia-infected male no longer leads to normal embryo development. As early as the first zygotic division, the paternal chromatin shows remodelling defects and fails to condense and segregate properly, leading to aneuploid or haploid development, which is lethal in flies and mosquitoes.
    We are interested in CI molecular bases in order to understand how Wolbachia can modify the sperm characteristics and how their presence also in infected eggs restores the sperm-egg compatibility to allow normal development after fertilization by infected males.