2022-11-02| R&D

Bacteriophage Characteristics Could Provide the Key to Tackling Viruses

by Richard Chau
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A better understanding of microorganisms is important for understanding the properties and pathogenicity of pathogens. A recent study published in Frontiers in Microbiology found that some viruses seem to know how to use information from their environment to determine when to stay inside their hosts and when to multiply and burst out. Although viruses are currently using this ability for their own benefit, the team believes that in the future, humans may be able to use this to fight viruses.

Bacteriophages Have Binding Sites to Monitor CtrA Levels

In this latest study, the University of Maryland Baltimore County (UMBC) team noted some unusual features when looking at recently discovered bacteriophages (or simply “phages”). The phages in this study primarily infect bacteria of the order Caulobacterales, which exist in two forms: a “swarmer” form that swims around freely and a “stalked” form that attaches to a surface. Researchers found that the phages in this study can only infect their hosts when the bacterial cells are in the swarmer state when they have special appendages called pili and flagella that help the bacteria move and mate.

Caulobacterales are known to live in oligotrophic environments where nutrients are scarce, and they are very spread out. When they find a favorable microhabitat, they become stalked cells and proliferate, eventually producing large quantities of swarmer cells. The bacteria produce a transcriptional regulator called CtrA, a protein that controls when they generate pili and flagella. The research team discovered that many pilitropic (adsorb to bacterial pili) and flagellotropic (adsorb to flagella) phages have CtrA binding sites in their DNA. 

Ivan Erill, an associate professor at the Department of Biological Sciences of the UMBC and senior author of the new paper, highlighted that it is unusual for a phage to have a binding site for a protein produced by its host. The team further expanded their investigation and found that the CtrA protein binding sites are not unique to a single phage or a group of phages, but many different types of phages have CtrA binding sites, and the common feature of all these phages is that they can only infect hosts with pili and flagella.

Given the preference of these phages for cellular appendages and that CtrA levels fluctuate up and down during the cells’ life cycle, the team hypothesized that phages are monitoring CtrA levels to know the right timing to strike. It is in the best interest of the phages to choose to burst from their hosts when they find favorable microhabitats that allow the cells to become factories for the production of swarmer cells.

The researchers suggested that the ability to monitor CtrA levels in a wide range of phages targeting different bacteria represents an evolutionary process that has occurred many times and that this feature of “convergent evolution” of distantly related species often indicates the utility of this function.

Redefining Virus-Host Interactions

Although the hypothesis that phages monitor CtrA for optimal timing has yet to be confirmed, the team is convinced that there is no reasonable alternative to this hypothesis to explain the prevalence of CtrA binding sites in different phages. According to Ivan Erill, the biggest gain from this study is the knowledge that viruses use cellular intelligence to make decisions.

Erill also pointed out that given the current understanding of phages, every evolutionary strategy they have developed has been shown to be able to transform themselves into viruses that infect plants and animals. If phages are “listening” to their hosts, it is almost certain that the viruses that affect humans will do the same.

The team’s discovery also opens the door for new therapies, although there is still much work to be done. Take the development of antiviral drugs as an example; if scientists can confirm the hypothesis that viruses possess the ability to sense specific signals, it may be possible to exploit the ability to deceive viruses. Researchers are hoping to prove the hypothesis that viruses utilize CtrA proteins to find the optimal timing for cell lysis in the future and will continue to search for the presence of receptors for other bacterial regulatory molecules in phages.

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