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Phages, Plasmids, and Other Mobile Genetic Elements

Bacteriophages (phages for short) are obligate parasites of bacteria and play a crucial role in maintaining bacterial populations and shaping microbial communities. Phages also have the potential to selectively eliminate specific organisms across diverse fields such as healthcare, agriculture, and industry. Our research focuses on unraveling the rich diversity and ecology of phages across the earth’s environments.

Phages can range in size dramatically, and we have uncovered and cataloged clades of huge phages from across the earth’s ecosystems (1). We also study how phages interact with their host, with some being able to augment their host's metabolism through the incorporation of metabolic genes in the phage genome (2). By studying a large number of phages, we find that reassigned stop codons that are predicted to be incompatible with bacterial translation systems are frequent and have arisen independently many times (3). We postulated that this has evolved to prevent the premature production of late-stage proteins and premature cell lysis. Furthermore, our research has led to the discovery of phages encoding their own CRISPR-Cas machinery (4), which has demonstrated potential for genome engineering in plants and animals (5).

Our current work encompasses various aspects of virome dynamics and phage research. One focus is on utilizing strain-resolved metagenomics to explore the dynamics of the virome in both preterm and full-term infants, particularly in relation to vertical transmission from mothers to infants. Additionally, we are actively employing phage-based approaches to selectively eliminate specific organisms from microbial enrichment cultures. This allows us to investigate microbial interactions and the assembly of microbial communities. Furthermore, we are exploring the potential of phages as an alternative to antibiotics in community editing experiments. In parallel, we engage in computational analysis to mine phages and viruses, establishing connections with their microbial hosts. Through this, we aim to deepen our understanding of the evolutionary and ecological roles played by phages and viruses in microorganisms, as well as their impact on biogeochemical cycles involving carbon, nitrogen, sulfur, and other elements.

Plasmids represent another important group of mobile genetic elements, while their diversity and distribution have not yet been fully characterized. Currently, there is a huge bias surrounding the hosts of known plasmids; for example, very few have been identified as Archaea. Some plasmids may contain novel genes that could be used as genome editors, and some could be utilized to deliver proteins into cells. Our current work regarding plasmids focuses on the identification and discovery of plasmids from various habitats via metagenomic analyses. A practical pipeline is to combine both supervisor (reference-based) and non-supervisor (reference-independent) approaches.

 

We recently uncovered a novel group of enigmatic extrachromosomal mobile genetic elements (6), which we refer to as ‘Borgs’, that appear to occur exclusively within the methane-oxidizing bacterial genus of Mehtanoperedens. Encoded on the Borg genomes, which can exceed 1 Mbp in length, are proteins that are involved in methane metabolism. The ability of Borgs to augment or influence the metabolism of this climate-relevant microorganism may have far-reaching biogeochemical consequences. Given that a significant fraction of sequences from metagenomic analyses have poor taxonomic and functional annotation, we believe that there may exist more genetic elements like Borgs.

Relevant publications

[1] Al-Shayeb, B., Sachdeva, R., Chen, L.X., Ward, F., Munk, P., Devoto, A., Castelle, C.J., Olm, M.R., Bouma-Gregson, K., Amano, Y. and He, C., 2020. Clades of huge phages from across Earth’s ecosystems. Nature, 578(7795), pp.425-431.
[2] Chen, L.X., Méheust, R., Crits-Christoph, A., McMahon, K.D., Nelson, T.C., Slater, G.F., Warren, L.A. and Banfield, J.F., 2020. Large freshwater phages with the potential to augment aerobic methane oxidation. Nature microbiology, 5(12), pp.1504-1515.
[3] Borges, A.L., Lou, Y.C., Sachdeva, R., Al-Shayeb, B., Penev, P.I., Jaffe, A.L., Lei, S., Santini, J.M. and Banfield, J.F., 2022. Widespread stop-codon recoding in bacteriophages may regulate translation of lytic genes. Nature Microbiology, 7(6), pp.918-927.
[4] Al-Shayeb, B., Skopintsev, P., Soczek, K.M., Stahl, E.C., Li, Z., Groover, E., Smock, D., Eggers, A.R., Pausch, P., Cress, B.F. and Huang, C.J., 2022. Diverse virus-encoded CRISPR-Cas systems include streamlined genome editors. Cell, 185(24), pp.4574-4586.
[5] Pausch, P., Al-Shayeb, B., Bisom-Rapp, E., Tsuchida, C.A., Li, Z., Cress, B.F., Knott, G.J., Jacobsen, S.E., Banfield, J.F. and Doudna, J.A., 2020. CRISPR-CasΦ from huge phages is a hypercompact genome editor. Science, 369(6501), pp.333-337.

[6] Al-Shayeb, B., Schoelmerich, M.C., West-Roberts, J., Valentin-Alvarado, L.E., Sachdeva, R., Mullen, S., Crits-Christoph, A., Wilkins, M.J., Williams, K.H., Doudna, J.A. and Banfield, J.F., 2022. Borgs are giant genetic elements with potential to expand metabolic capacity. Nature, pp.1-6.

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