Cellular, molecular, and evolutionary mechanisms of Wolbachia stem cell niche tropism in Drosophila
Olsen, Michelle Toomey
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The intracellular bacteria Wolbachia infect up to 40% of all insect species, including the vectors of prevalent infectious diseases such as Dengue and malaria. Even though Wolbachia infections are the largest pandemic on this planet, the cellular and molecular mechanisms for bacterial spreading in nature are still unknown. Wolbachia are mainly vertically transmitted through the egg cytoplasm, however there is also evidence of extensive horizontal transmission. We have found that Wolbachia target the stem cell niches in the Drosophila ovary to enhance germline colonization and subsequent vertical transmission. This tropism is pervasive across the Drosophila genus, with the pattern of targeting being evolutionarily conserved. Phylogenetic analyses, confirmed by hybrid introgression and transinfection experiments, demonstrate that bacterial factors are the major determinants of differential patterns of niche tropism. Furthermore, bacterial load is increased in germline cells passing through infected niches, supporting previous findings suggesting a contribution of Wolbachia from stem cell niches towards vertical transmission. If niche tropism is important for Wolbachia transmission through the germline, evolutionary theory predicts that there should be no selective pressure to maintain niche tropism in males. Indeed, we have found that tropism to the stem cell niche in the testis, known as the hub, is not evolutionarily conserved. Towards identifying the cellular and molecular mechanisms of stem cell niche tropism, we investigated hub targeting of closely related Wolbachia strains (wMel-like strains: wMel, wMel2, and wMel3; wMelCS-like strains: wMelCS, wMelCS2, and wMelPop). wMel-like and wMelCS-like Wolbachia strains differ in their frequencies and densities of hub infection. The targeting differences of these strains of Wolbachia indicate that this phenotype is rapidly evolving, as they shared a common ancestor only 8,000 years ago. With the plethora of tools available in D. melanogaster, a candidate gene approach was used to target host proteins enriched in the stem cell niche in the testis for RNAi mediated gene knockdown in the hub. We have identified Drosophila stem cell related signaling pathways that promote Wolbachia accumulation. Unraveling the cellular and molecular bases of tissue tropism is fundamental to understanding Wolbachia-host interactions.