Abstract
A wide variety of maternally transmitted endosymbionts in insects are associated with reproductive parasitism, whereby they interfere with host reproduction to increase the ratio of infected females and spread within populations.[1][,][2] Recent successes in identifying bacterial factors responsible for reproductive parasitism[3][,][4][,][5][,][6][,][7] as well as further omics approaches[8][,][9][,][10][,][11][,][12] have highlighted the common appearance of deubiquitinase domains, although their biological roles-in particular, how they link to distinct manipulative phenotypes-remain poorly defined. Spiroplasma poulsonii is a helical and motile bacterial endosymbiont of Drosophila,[13][,][14] which selectively kills male progeny with a male-killing toxin Spaid (S. poulsonii androcidin), which encodes an ovarian tumor (OTU) deubiquitinase domain.[6] Artificial expression of Spaid in flies reproduces male-killing-associated pathologies that include abnormal apoptosis and neural defects during embryogenesis[6][,][15][,][16][,][17][,][18][,][19]; moreover, it highly accumulates on the dosage-compensated male X chromosome,[20] congruent with cellular defects such as the DNA damage/chromatin bridge breakage specifically induced upon that chromosome.[6][,][21][,][22][,][23] Here, I show that without the function of OTU, Spaid is polyubiquitinated and degraded through the host ubiquitin-proteasome pathway, leading to the attenuation of male-killing activity as shown previously.[6] Furthermore, I find that Spaid utilizes its OTU domain to deubiquitinate itself in an intermolecular manner. Collectively, the deubiquitinase domain of Spaid serves as a self-stabilization mechanism to facilitate male killing in flies, optimizing a molecular strategy of endosymbionts that enables the efficient manipulation of the host at a low energetic cost.
