Type III CI factors from wAlbB induce cytoplasmic incompatibility via a Host Modification mechanism
- 1Temasek Life Sciences Laboratory, National University of Singapore, University Hall, Singapore
- 2Department of Biological Sciences, National University of Singapore, University Hall, Singapore
Abstract
The widespread prevalence of the endosymbiotic bacterium Wolbachia among insect species relies on its ability to invade and manipulate host reproduction via several ways, among which cytoplasmic incompatibility (CI) is most studied. Two non-mutually exclusive models, the Host-Modification (HM) and the Toxin-Antidote (TA), have been proposed to explain the molecular basis of CI. Here, we investigate the CI-inducing activity of the Type III CI factors (cifs) from wAlbB, a strain currently being deployed to combat mosquito-borne diseases. This set of Cifs displays conserved subcellular localization dynamics in various insect cells. Both cifA and cifB are required for the induction of DNA damage in cultured cells, and transgenic Drosophila. Moreover, these cifs induce CI in Drosophila through the two-by-one manner, meaning cifA and cifB act together during spermatogenesis to induce CI, and maternal cifA can reverse the effect. Mechanistically, genetic, biochemical, cellular, and proteomic analyses reveal that this pair of cifs acts during the early stage of spermatogenesis but is dispensable in late-stage germline cells for CI induction. Collectively, our findings support the notion that wAlbB Type III cifs induce CI via a HM-based mechanism. Additional analyses suggest that different Wolbachia strains may employ distinct molecular mechanisms to induce CI. Author summary: Mosquito-borne diseases remain a major global health challenge, infecting hundreds of millions of people and causing hundreds of thousands of deaths each year. Wolbachia-based vector control is a promising strategy for reducing transmission of these pathogens and is currently being implemented in dozens of countries. This approach relies on cytoplasmic incompatibility (CI), a form of reproductive manipulation imposed by Wolbachia. Although the genes responsible for CI, known as CI factors (cifs), have been identified, the molecular mechanism underlying CI has remained controversial. We show here that Type III cifs from wAlbB induce CI through a Host Modification mechanism. We further provide evidence that different Wolbachia strains may use distinct molecular mechanisms to induce CI, with important implications for understanding and improving Wolbachia-based disease control strategies.
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BibTeX
@article{hou2026type,
title = {{Type III CI factors from wAlbB induce cytoplasmic incompatibility via a Host Modification mechanism}},
author = {Xinjun Hou and Feng Guang Goh and Sen Liu and Yao Liu and Xin Ee Yong and Qingsong Lin and Yu Cai},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014760},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014760},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Type III CI factors from wAlbB induce cytoplasmic incompatibility via a Host Modification mechanism
AU - Xinjun Hou
AU - Feng Guang Goh
AU - Sen Liu
AU - Yao Liu
AU - Xin Ee Yong
AU - Qingsong Lin
AU - Yu Cai
PY - 2026
DA - 2026/10/29
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014760
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014760
AB - The widespread prevalence of the endosymbiotic bacterium Wolbachia among insect species relies on its ability to invade and manipulate host reproduction via several ways, among which cytoplasmic incompatibility (CI) is most studied. Two non-mutually exclusive models, the Host-Modification (HM) and the Toxin-Antidote (TA), have been proposed to explain the molecular basis of CI. Here, we investigate the CI-inducing activity of the Type III CI factors (cifs) from wAlbB, a strain currently being deployed to combat mosquito-borne diseases. This set of Cifs displays conserved subcellular localization dynamics in various insect cells. Both cifA and cifB are required for the induction of DNA damage in cultured cells, and transgenic Drosophila. Moreover, these cifs induce CI in Drosophila through the two-by-one manner, meaning cifA and cifB act together during spermatogenesis to induce CI, and maternal cifA can reverse the effect. Mechanistically, genetic, biochemical, cellular, and proteomic analyses reveal that this pair of cifs acts during the early stage of spermatogenesis but is dispensable in late-stage germline cells for CI induction. Collectively, our findings support the notion that wAlbB Type III cifs induce CI via a HM-based mechanism. Additional analyses suggest that different Wolbachia strains may employ distinct molecular mechanisms to induce CI. Author summary: Mosquito-borne diseases remain a major global health challenge, infecting hundreds of millions of people and causing hundreds of thousands of deaths each year. Wolbachia-based vector control is a promising strategy for reducing transmission of these pathogens and is currently being implemented in dozens of countries. This approach relies on cytoplasmic incompatibility (CI), a form of reproductive manipulation imposed by Wolbachia. Although the genes responsible for CI, known as CI factors (cifs), have been identified, the molecular mechanism underlying CI has remained controversial. We show here that Type III cifs from wAlbB induce CI through a Host Modification mechanism. We further provide evidence that different Wolbachia strains may use distinct molecular mechanisms to induce CI, with important implications for understanding and improving Wolbachia-based disease control strategies.
SN - 1553-7374
ER -