Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito

Wolbachia infections are a fascinating example of reproductive parasitism with strong potential to combat vector-borne diseases, due to their combined ability to spread in insect populations and block pathogen replication. Though the Wolbachia factors mediating the notable reproductive manipulation cytoplasmic incompatibility (CI) have now been identified as prophage WO genes cifA and cifB, the relative role of these genes is still intensely debated, with different models claiming that CI requires either both factors or cifB alone. Here we investigated whether cifA and cifB are sufficient to induce conditional sterility in the major malaria vector Anopheles gambiae, a species that appears to have limited susceptibility to invasion by Wolbachia. We report that CI can be fully recapitulated in these mosquitoes, and that cifB is sufficient to cause this reproductive manipulation. cifB-induced sterility is fully rescued by high levels of cifA expression in females. Surprisingly, however, when cifA is highly expressed in males alongside cifB, the CI phenotype is attenuated. cifB strongly impairs fertility also when expressed in the female germline, again mitigated by cifA. These data support a system whereby cifB and cifA must be fine-tuned to exercise CI and rescue, respectively, possibly explaining the limited success of Wolbachia at invading Anopheles. Our findings pave the way towards facilitating Wolbachia infections in anopheline vectors, for use in malaria control strategies.