Viruses Found to Utilize Environmental Cues Before Lysogenic Cycle

Bacteriophages, or “phages,” are viruses that infect bacteria and are commonly used for research on antiviral drug development. Phages move around the extracellular space with their pili and flagella, and a specific protein called CtrA is responsible for these appendages’ generation and movement. New research from the University of Maryland, Baltimore County revealed that many phages have binding sites for CtrA within their genome, requiring their hosts to have pili or flagella for infection.  

A virus’s ability to sense its environment, including elements produced by its host, adds “another layer of complexity to the viral-host interaction,” says Ivan Erill, senior author and professor of biological sciences at UMBC. The first phage the team identified CtrA binding sites infects a specific group of bacteria called Caulobacterales. This bacterium exists in two forms: a “swarmer” form that swims around freely and a “stalked” form that must be anchored to a surface. The swarmers have pili and flagella, but the stalks do not.

CtrA regulates the cell cycle in both bacterial forms, determining whether a cell divides evenly into two of the same cell type or divides unevenly to produce a swarmer and a stalk cell. Since bacteriophages can only infect swarmer cells, it's in their best interest to burst out of host cells when additional swarmer cells are available nearby for infection. “But when they find a good pocket of microhabitat, they become stalked cells and proliferate,” says Erill, eventually producing large quantities of swarmer cells.

 “We hypothesize the phages are monitoring CtrA levels, which go up and down during the life cycle of the cells, to figure out when the swarmer cell is becoming a stalk cell and becoming a factory of swarmers,” Erill continues, “and at that point, they burst the cell, because there are going to be many swarmers nearby to infect.”

For future work, Erill and colleagues want to tackle the detailed methodology required to support their hypothesis. There are a few documented examples of phages monitoring their environment in unique ways, but none include numerous different phages employing the same strategy against bacterial hosts. Additionally, members of his lab are already looking for receptors for other bacterial regulatory molecules in phages.

The team also notes that these findings may have implications on viruses infecting other organisms, even humans. “Everything that we know about phages, every single evolutionary strategy they have developed, has been shown to translate to viruses that infect plants and animals,” he says. “It’s almost a given. So if phages are listening in on their hosts, the viruses that affect humans are bound to be doing the same.”

This research’s key takeaway, according to Erill, is that “the virus is using cellular intel to make decisions, and if it’s happening in bacteria, it’s almost certainly happening in plants and animals, because if it’s an evolutionary strategy that makes sense, evolution will discover it and exploit it.”

The findings were recently published in the journal Frontiers in Microbiology.