Wolbachia endosymbionts manipulate the self-renewal and differentiation of germline stem cells to reinforce fertility of their fruit fly host

The alphaproteobacterium Wolbachia pipientis infects arthropod and
nematode species worldwide, making it a key target for host biological
control. Wolbachia-driven host reproductive manipulations, such as
cytoplasmic incompatibility (CI), are credited for catapulting these
intracellular bacteria to high frequencies in host populations. Positive,
perhaps mutualistic, reproductive manipulations also increase infection
frequencies, but are not well understood. Here, we identify molecular and
cellular mechanisms by which Wolbachia influences the molecularly distinct
processes of germline stem cell (GSC) self renewal and differentiation. We
demonstrate that wMel infection rescues the fertility of flies lacking the
translational regulator mei-P26, and is sufficient to sustain infertile
homozygous mei-P26-knockdown stocks indefinitely. Cytology revealed that
wMel mitigates the impact of mei-P26 loss through restoring proper pMad,
Bam, Sxl, and Orb expression. In Oregon R files with wild-type fertility,
wMel infection elevates lifetime egg hatch rates. Exploring these
phenotypes through dual-RNAseq quantification of eukaryotic and bacterial
transcripts revealed that wMel infection rescues and offsets many gene
expression changes induced by mei-P26 loss at the mRNA level. Overall, we
show that wMel infection beneficially reinforces host fertility at mRNA,
protein, and phenotypic levels, and these mechanisms may promote the
emergence of mutualism and the breakdown of host reproductive
manipulations.