Deubiquitylases and nucleases in bacterial symbiont-induced cytoplasmic incompatibility.

In myriad arthropod species, maternally transmitted symbiotic bacteria spread through populations by manipulating host reproduction, most frequently by a mechanism called cytoplasmic incompatibility (CI). CI occurs when bacterially infected males fertilize uninfected females, typically causing paternal chromatin condensation and segregation defects and usually embryonic arrest in the first zygotic cell cycle. Embryos survive if the female is similarly infected, which promotes bacterial spread. The endosymbiont best known for CI is Wolbachia, now widely used against mosquitoes that vector viral diseases such as dengue fever. Although CI is induced by Wolbachia resident in testes, mature sperm carry no bacteria, indicating they alter sperm in a way that, following fertilization, interferes with embryogenesis. CI-inducing factors (Cifs) are expressed from syntenic Wolbachia cifA-cifB genes. CifB is required in the male germline to induce CI, while CifA expression in the host female is sufficient to rescue viability. Importantly, CifA suppresses lethality through its binding to CifB. Different CifB proteins have distinct CI-relevant enzymatic functions, in particular, deubiquitylase and nuclease activities. Consistent with these genetic data, CifB is packaged into sperm during spermiogenesis. While sperm morphological disruption has been observed in fruit flies carrying cif transgenes, a causal role in CI is unclear. Also not understood is how maternally provisioned CifA rescues embryo viability. Exciting new findings with diverse symbiotic bacteria reveal cifA-cifB-like operons on extrachromosomal plasmids. These results suggest far wider deployment of Wolbachia-related CI factors than previously thought and multiple mechanisms for lateral cif gene transfer.