Marine bacterium uses molecular signals to control a latent virus

Bacteria are subject to virus infections just like all other organisms, and it is estimated that viruses kill up to half of all bacteria in the oceans. With an average size of 0.0001 millimeter and an estimated abundance of 10³¹, these viruses of bacteria, so-called bacteriophages, are the smallest and most numerous biological entities on Earth.

They are small, but their effect on the planet’s ecosystems is substantial. Due to their extensive killing of bacteria, they constitute a major driving force in the turnover of nutrients in the environment. Bacteriophages also affect the community composition and diversification of bacteria by selectively infecting some bacterial species while sparing others, and by acting as vehicles for horizontal gene transfer between bacteria.

Many types of bacteriophages can enter a dormant state, during which the genetic material of the virus is incorporated into the genome of the infected host bacterium. Such an infected bacterium continues to live, now with a new, expanded repertoire of genes. As such, the virus is present as a latent genetic time bomb in the bacterium, which can be activated at a future point. When viral activation happens, virus particles are produced inside the bacterial host, the host is killed, and the viruses can spread to neighboring bacteria.

- ”Whether these latent viruses are activated is of course critical for a bacterial population. Therefore, we are eager to understand which conditions can lead to their activation”, says associate professor Sine Lo Svenningsen of the Biomolecular Sciences Section.

Until now, studies of the mechanisms that activate latent viruses have taken offset in the hypothesis that viruses are evolutionarily tuned to do what promotes their own spread, irrespective of the cost for the infected bacterial populations. But the new research from the Department of Biology reveals that the marine fish pathogen Vibrio anguillarum has evolved the means to take control over the activation of a latent virus.

Vibrio anguillarum secretes signal molecules into its surroundings, and uses these chemical signals to gain information about the size and density of the bacterial population it is part of. If many bacteria grow in close proximity and all produce the signal molecules, the concentration of the signals will increase, and the bacteria can detect that. The chemicals thereby function as signals to individual bacteria, informing them that they are members of a densely populated bacterial community.

-“What is surprising about the new research is that these signal molecules control the life cycle of a latent virus which is widespread among Vibrio anguillarum bacteria, and they prevent viral activation when the bacterial community is densely populated. Instead, the virus is activated in a small fraction of the members of bacterial communities when they are only sparsely populated”, explains Professor Mathias Middelboe from the Section for Marine Biology.

But if the bacterial hosts can control the virus, why have they not evolved to block viral activation at all times? To answer this question, the researchers investigated whether it could be advantageous for the bacterial population as a whole to allow viral activation in some of its members under certain conditions.

- ”We compared bacterial populations that carried the latent viruses with otherwise identical populations that didn’t, and we found that when the bacterial communities were too sparsely populated to detect the signal molecules, the communities that carried the viruses were much better at forming protective aggregates called biofilm”, says Mette Burmølle, Associate Professor at the Section for Microbiology.

The formation of biofilm is a prerequisite for Vibrio anguillarum to infect fish. Mette Burmølle continues:

- ”The correlation between viral activation and formation of biofilm is presumably caused by the release of organic material happening when viruses kill their host bacteria. The material helps the remaining bacteria stick together in aggregates. For this reason, it can be advantageous for the bacterial population to sacrifice some individual bacteria as long as the density of surrounding bacteria is low.”

The researchers have shown that, in this case, the traditional roles are reversed between virus and host organism, which also changes our understanding of bacteriophage-host interactions: By placing the latent virus that is incorporated in the bacterial genome under the control of the bacterial signal molecules, the bacterial population can to some extent control activation of the virus, and sacrifice part of the population to make biofilm when the density of bacteria is low. On the other hand, when the bacterial density is high, the signal molecules prevent activation of the virus, thereby preventing rapid spread of the virus in the population.