Wolbachia endosymbionts manipulate GSC self-renewal and differentiation to enhance host fertility

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 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 OreR files with wild-type fertility, wMel infection elevates lifetime egg hatch rates. Exploring these phenotypes through dual-RNAseq experiments 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. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/520626v2_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@151904corg.highwire.dtl.DTLVardef@1d86e41org.highwire.dtl.DTLVardef@2e768eorg.highwire.dtl.DTLVardef@697109_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights[bullet] The wMel strain of Wolbachia restores fertility in females and males deficient for the essential translational regulator meiotic-P26 [bullet]Mei-P26s germline maintenance and oocyte cyst differentiation functions are genetically rescued by wMel infection [bullet]Perturbed pMad, Sxl, Bam, and Orb protein expression are mitigated by wMel infection [bullet]wMel infection elevates lifetime egg lay and hatch rates in OreR flies [bullet]Ovary transcriptomes reveal wMel infection restores or offsets changes in gene expression induced by the loss of functional mei-P26 Significance StatementWolbachia bacterial symbionts are being harnessed as biological control agents through the use of their costly manipulations to host fertility. Here, we reveal that the wMel strain can have a beneficial impact on fruit fly development in both mutant and wild-type flies. This phenotype is essential to the long-term use of these bacteria for host population control.