Welcome to the Bacteriophage WO Project that seeks knowledge and applications from a common virus of the world’s most widespread animal-associated symbiont: Wolbachia.
Select Media
- How does a virus hijack insect sperm to control disease vectors and pests? Penn State Research News (3/8/24)
- Beyond Wolbachia – Can a small molecule control insect reproduction? Cell Reports Preview (10/28/25)
Research Summary
Bacterial viruses, or bacteriophages, are among the most abundant and diverse biological entities on the planet with the most genes new to biology. Bacteriophages are typically studied in free-living or host-associated bacteria where they are renowned for vectoring virulence genes, diversifying bacterial genomes, and phage therapy applications. However, they are rarely studied in obligate endosymbiotic bacteria that fastidiously live inside the cells of their hosts. Over the past two decades, we developed phage WO of Wolbachia as a model system for phage biology in symbionts. We determined how phage WO thrives and functions in this specialized, symbiotic niche, what adaptive capacities it bestows to Wolbachia including the long-sought genes underpinning cytoplasmic incompatibility and male killing. We translate this knowledge to various vector control applications for human and agricultural health.
A major area of investigation is how phage WO contributes to Wolbachia‘s cunning parasitism of animal reproduction. These parasitic strategies include a sperm-egg incompatibility termed cytoplasmic incompatibility and the selective killing of male embryos, which both contributed to spreading Wolbachia to become the most common bacterial symbiont in the animal world. They do so by parasitically increasing the fitness of females – the transmitting sex for Wolbachia. We discovered the phage WO genes cifA and cifB genes that underpin cytoplasmic incompatibility by Wolbachia, and we aim to utilize these genes to control agricultural pests and mosquito-borne diseases (video link 1 and 2). We also identified the wmk gene that is a candidate for male killing. wmk is a just a few genes away from the cifA and cifB genes in the phage WO Eukaryotic Association Module that is enriched with other genes predicted to interact directly with host eukaryotic biology.
To the best of our knowledge, few if any studies in virology have assessed the potential for viruses to traverse multiple cellular domains of life. Phage WO is a quintessential example whose secrets continue to bear fruit for the study of the most widespread symbiosis on the planet.
Select Research Publications
- Kaur, R., A. McGarry, J.D. Shropshire, B.A. Leigh, and S.R. Bordenstein (2024) Prophage proteins alter long noncoding RNA and DNA of developing sperm to induce a paternal-effect lethality. Science 383:6687 1111-1117
- Kaur, R., B.A. Leigh, I.T. Ritchie, and S.R. Bordenstein (2022) The Cif proteins from Wolbachia prophage WO modify sperm genome integrity to establish cytoplasmic incompatibility. PLOS Biology 20(5): e3001584. https://doi.org/10.1371/journal.pbio.3001584
- Perlmutter, J.I. , J.E. Meyers, S.R. Bordenstein (2021) A single synonymous nucleotide change impacts the male-killing phenotype of prophage WO gene wmk. eLife 10:e67686
- Shropshire, J.D., J. On, E.M. Layton, H. Zhou, S.R. Bordenstein (2018) One prophage WO Gene Rescues Cytoplasmic Incompatibility in Drosophila melanogaster. Proceedings of the National Academy of Sciences https://doi.org/10.1073/pnas.1800650115
- Lepage, D., J.A. Metcalf, S.R. Bordenstein, J. On, J. Perlmutter, J.D. Shropshire, E. Layton, J. Beckmann, and S.R. Bordenstein (2017) Prophage WO Genes Recapitulate and Enhance Wolbachia-Induced Cytoplasmic Incompatibility. Nature 10.1038/nature21391
- Bordenstein SR and SR Bordenstein (2016) Eukaryotic Association Module in Phage WO Genomes from Wolbachia. Nature Communications 7: 13155.
Select Reviews
- Kaur, R., J.D. Shropshire, K.L. Cross, B. Leigh, A.J. Mansueto, V. Stewart, S.R. Bordenstein, and S.R. Bordenstein (2021) Living in the Endosymbiotic World of Wolbachia: A Centennial Review. Cell Host & Microbe
- Shropshire JD, B Leigh, and SR Bordenstein (2020) Symbiont-Mediated Cytoplasmic Incompatibility: What Have We Learned in 50 Years? eLife
- Metcalf JA and SR Bordenstein (2012) The Case of Endosymbionts: The Complexity of Virus Systems. Current Opinion in Microbiology 15(4): 546-552.
- Kent BN and SR Bordenstein (2010) Phage WO: Lamda of the Endosymbiont World. Trends in Microbiology 18(4):173-81.
