Male-killing toxin in a bacterial symbiont of Drosophila

Abstract

Several lineages of symbiotic bacteria in insects selfishly manipulate host reproduction to spread in a population1, often by distorting host sex ratios. Spiroplasma poulsonii2,3 (hereafter Spiroplasma) is a helical and motile, Gram-positive symbiotic bacterium, that resides in a wide range of Drosophila species4. A striking feature of Spiroplasma is male killing, whereby the sons of infected female hosts are selectively killed during development1,2. Although male killing caused by Spiroplasma has been studied since the 1950s, the underlying mechanism is unknown. Here, we identify a Spiroplasma protein, designated SpAID, whose expression induces male killing. Overexpression of SpAID in D. melanogaster kills males but not females, and induces massive apoptosis and neural defects, recapitulating the pathology observed in Spiroplasma-infected male embryos5–11. Our data suggest that SpAID targets the dosage compensation machinery on the male X chromosome to mediate its effects. SpAID contains ankyrin repeats and a deubiquitinase domain, which are required for its subcellular localization and activity. Moreover, we found a laboratory mutant strain of Spiroplasma with reduced male-killing ability and a large deletion in the SpAID locus. Collectively, our study has uncovered a novel bacterial protein that affects host cellular machinery in a sex-specific way, which is likely to be the long-searched-for factor responsible for Spiroplasma-induced male killing.