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Bacteriophage genomics and functions

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

Recent Media Coverage

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 parasitism of animal reproduction. These parasitic strategies include cytoplasmic incompatibility and male-killing, which facilitate the spread of Wolbachia through their host populations. We recently discovered the cifA and cifB genes that underpin cytoplasmic incompatibility, and we aim to utilize these genes to control agricultural pests and mosquito-borne diseases (video link 1 and 2). cifA and cifB codiverge and occur in phage WO’s Eukaryotic Association Module that is enriched with snippets of animal DNA and large genes predicted to interact with animal hosts.

Select Publications

  • Perlmutter, J.I.  S.R. Bordenstein, D.P. LePage, J.A. Metcalf, T. Hill, J. Martinez, R.L. Unckless, F.M. Jiggins, and S.R. Bordenstein (2019) The phage gene wmk is a candidate for male killing by a bacterial endosymbiont. PLOS Pathogens 15(9): e1007936 Paper
  • 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
  • Kent BN and SR Bordenstein (2010) Phage WO: Lamda of the Endosymbiont World. Trends in Microbiology 18(4):173-81. Paper