Vanderbilt School of Medicine | Vanderbilt University | Vanderbilt Medical Center

Welcome to the Bacteriophage WO Project that seeks knowledge and applications from a common virus of Wolbachia.


Media Coverage and Info

Unraveling genetic mystery next step in Zika and dengue fight Vanderbilt Research News (4/23/18)

New Tool for Combating Mosquito-Borne Disease: Insect Parasite Genes Vanderbilt Research News (2/27/17)

What This Itsy Bitsy Virus Took From a Spider CNN report (10/18/16)

This Week in Virology Podcast / Video (4/12/15)

Taking the Bite Out of Vector-Borne Diseases NIH press release (03/27/13)

Scientist: "Symbiotic Enemies Fight Over Insect" (March 2006)


Research Summary

Bacterial viruses, or bacteriophages, are among the most abundant biological entites on the planet and encode a vast amount of novel genes. Bacteriophages are typically studied in free-living or host-associated bacteria, but are rarely studied in obligate intracellular bacteria that fastidiously live inside the cells of their hosts, such as plants and animals. We have developed phage WO of Wolbachia as a model system for phages that live within the cells of animals hosts. We seek to determine how phage WO thrives and functions in this specialized, symbiotic niche and then translate this knowledge to various biomedical or entomological applications.

Obligate intracellular baceria like Wolbachia are encompassed by both bacterial and eukaryotic membranes, and therefore phage WO may possess an enigmatic two-fold challenge. Phage WO must not only breach peptidoglycan and permeabilize bacterial membranes, but they also have to cross the eukaryotic membrane(s) that encapsulates the bacteria as well as the eukaryotic cytoplasm or extracellular matrix that they encounter upon bacterial lysis. To the best of our knowledge, no study in virology has assessed the potential for viruses to traverse multiple cellular domains of life. Do these viruses thrive with standard bacteriophage genes or do they utilize a novel strategy that transcends contemporary virus demarcations? Answers to these questions led us to the discovery and characterization of the Eukaryotic Association Module of phage WO.

Another major area of investigation is how phage WO contributes to Wolbachia's cunning ways of altering reproductive strategies of arthropods. These manipuatlions of reproduction include cytoplasmic incompatibility and male-killing, which facilitate the spread of phage WO and Wolbachia through their host populations. We recently discovered the cifA and cifB genes in the Eukaryotic Association Module of phage WO that enable cytoplasmic incompatibility, and we wish to utilize these genes to control agricultural pests and mosquito-borne diseases (video link 1 and 2).


Selected Publications

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 Paper

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 doi: Paper

Bordenstein SR and SR Bordenstein. (2016) Eukaryotic Association Module in Phage WO Genomes from Wolbachia. Nature Communications 7: 13155. Paper

Metcalf JA and SR Bordenstein. (2012) The Case of Endosymbionts: The Complexity of Virus Systems. Current Opinion in Microbiology 15(4): 546-552. Paper

Kent, B.N., L. Salichos, J.G. Gibbons, A. Rokas, I.L.G. Newton, M.E. Clark, and S.R. Bordenstein. (2011) Complete bacteriophage transfer in a bacterial endosymbiont (Wolbachia) determined by targeted genome capature. Genome Biology and Evolution (cover). Paper

Bordenstein, SR and Bordenstein SR. (2011) Temperature Affects the Tripartite Interactions Between Bacteriophage WO, Wolbachia, and cytoplasmic inocompatibilty. PLoS ONE 6(12): e29106. Paper

Kent BN and SR Bordenstein (2010) Phage WO: Lamda of the Endosymbiont World. Trends in Microbiology 18(4):173-81. Paper