Using metagenomics as a treasure map

Isolation of an elusive phage capable of enhancing cyclic electron flow in infected marine cyanobacteria

Go to the profile of Oded Beja
Aug 07, 2017
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The paper in Nature Microbiology is here:

Ever since we reported the existence of uncultured cyanophages containing photosystem-I genes (Sharon et al., 2009), we were determined to isolate them somehow. We knew that only in culture the hypotheses we poised regarding this phenomenon (Philosof et al. 2011) could be tested. However, we did not have any clue who their hosts where, nor did we know where and when to collect these phages. The little we did know was based on metagenomics, which provided us with some initial hints we could use as a map in our “treasure” hunt.

One such hint was a strong metagenomic signal found in samples from the equatorial Pacific Ocean. We were able to further narrow down our search area when we saw a clear PCR signal of these uncultured viruses when we checked water samples from the remote Line Islands. This signal, however, did not appear in all samples. We then collected viral concentrates off the shores of these islands. These precious 300 ml phage concentrates traveled all the way to our labs in Haifa where we anxiously awaited to find out whether they still contain infectious viral particles? Are the phages we are looking for there?

While we did not know who the hosts of these phages are, metagenomics provided a second hint. The genomic analysis of the metagenomic fragments gave us a good reason to presume that the likely hosts are marine cyanobacteria, Synechococcus or Prochlorococcus. Some 18 different cyanobacterial strains, the entire culture collection that was available in the lab at the time, were used for isolating the phage. Each cyanobacterial strain was challenged separately with the samples from the Line Islands. Lysis of infected cyanobacteria, caused by phages, was observed in some cultures but was not caused by the phages we were looking for. Finally, after a careful examination of the lysed cultures, the correct PCR signals were observed in a single strain of Prochlorococcus – the last strain we checked. This breakthrough led, eventually, to the isolation of P-TIM68 – a cyanophage containing the photosynthetic genes that were previously observed only via metagenomics (Sharon et al. 2009, Alprovitch et al. 2011).

We reported our initial metagenomic observations in 2009. Now, eight years later in 2017 we can finally report on this unique cyanophage. It took our international team (France, Spain, USA, and Israel) quite some time to culture this virus and even more time to understand the way it rewires host photosynthesis. We are now left with even more questions regarding the process by which these viruses use the photosynthetic genes they harbor to switch host photosynthesis into cyclic photosynthesis. Moreover, the exact influence of phages that carry photosystem I and II genes in the environment still remains to be answered.

Our Nature Microbiology paper is here:

Our work is dedicated to the memory of Prof. Fabrice Rappaport (Institut de Biologie Physico-Chimique, CNRS), who sadly passed away before the paper was finalized


Sharon, I., Alperovitch, A., Rohwer, F., Haynes, M., Glaser, F., Atamna-Ismaeel, N. Pinter, R.Y., Partensky, F., Koonin, E.V., Wolf Y.I., Nelson, N. and Béjà, O. (2009) Photosystem-I gene cassettes are present in marine virus genomes. Nature 461: 258-262.

Philosof, A., Battchikova, N., Aro, E.-M., and Béjà, O. (2011) Marine cyanophages: Tinkering with the electron transport chain. ISME J. 5: 1568-1570.

Alperovitch, A., Sharon, I., Rohwer, F., Aro, E.-M., Milo, R., Nelson, N., and Béjà, O. (2011) Reconstructing a puzzle: Existence of cyanophages containing both photosystem-I & photosystem-II gene-suites inferred from oceanic metagenomic datasets. Environ. Microbiol. 13: 24-32.


Go to the profile of Oded Beja

Oded Beja

Professor, Biology, Technion


Go to the profile of Paul Carini
Paul Carini 13 days ago

Cool paper and story!