Abstract

Significance Mosquito-borne diseases cause more than 700,000 deaths annually. Wolbachia pipientis , an intracellular bacterium infecting many insect species, can manipulate host reproduction through cytoplasmic incompatibility (CI) and is being used in several promising strategies for controlling mosquito populations and reducing the spread of mosquito-vectored viruses. Although the key factors involved in CI (called CI factors or Cifs) have been identified, the molecular mechanisms of CI induction and rescue remain elusive. We present comprehensive structural, biochemical, and functional studies on two major types of CI systems and demonstrate the importance of Cif complex formation for rescuing CI. Our findings lay the foundation for understanding the molecular mechanisms of CI and the engineering of Cifs to control agricultural pests and arthropod-borne human pathogens.

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