EDITOR’S CHOICE IN MICROBIOLOGY
The paper
M. Jahn et al., “A phage protein aids bacterial symbionts in eukaryote immune evasion,” Cell Host Microbe, 26:542–50, 2019.
While studying sponges and their endosymbiotic microbes for his PhD, Martin Jahn found himself pondering where viruses fit into the mix. “We didn’t know anything about the viruses associated with sponges,” says Jahn, now wrapping up his doctorate at the GEOMAR Helmholtz Centre for Ocean Research Kiel in Germany.
To investigate, Jahn and his colleagues sampled four sponge species off the coast of northern Spain and analyzed both the sponges and samples of the surrounding seawater for the presence of viruses. Not only did the researchers find viruses living in sponges that weren’t in the seawater, they discovered substantial diversity in the viromes of different species, and even among conspecifics.
Digging further into the genomic data, the team noticed one group of previously unidentified bacteriophages that were particularly abundant in sponge viromes. To Jahn’s surprise, these phages contained genetic sequences for so-called ankyrin repeats, protein motifs usually studied in bacteria that help pathogenic or commensal microbes infect and manipulate eukaryotic hosts. He wondered if the viruses, which the team dubbed ankyphages, might facilitate interactions between sponges and their resident bacteria.
Both sponge cells and their endosymbiotic bacteria are difficult to culture, so to test Jahn’s idea, the team set up an experiment with mouse cell lines and E. coli. The researchers first cultured E. coli with ankyrin protein synthesized from the viral sequences. Then they added the bacteria, which displayed the protein on their cell surfaces, to murine immune cells.
Sure enough, the E. coli that had been cultured with ankyrin protein were better at surviving exposure to mouse immune cells: they escaped being engulfed by macrophages more often than control bacteria did. E. coli engineered to produce and secrete the phage proteins themselves also survived macrophage exposure. The team ran further experiments to confirm that the protein wasn’t toxic to either the bacterial or murine cells, and concluded that phage-derived ankyrin was indeed helping to suppress macrophage responses toward the bacteria.
“I was quite impressed by these . . . proteins being associated with sponge-specific phage communities,” says Breck Duerkop, a microbiologist at the University of Colorado School of Medicine who wasn’t involved in the work. That phages might moderate host immunity is a “really interesting idea,” he adds, although the team’s experiments don’t quite establish that such three-way interactions are playing an important role in sponges.
Scanning genome databases for other phyla, Jahn and his colleagues found evidence that ankyphages are also present in the microbiomes of other eukaryotic organisms, including humans. The findings hint at the importance of bacteriophages in eukaryotic function, says Jahn. Far from being incidental stowaways in eukaryotic organisms, phages “are central elements,” he says. “It opens a lot of perspective for further research.”