New research led by UMBC Frontiers in Microbiology Viruses use information from their environment to indicate when to settle in their host and when to replicate and burst and kill the host’s cell. The work has implications for antiviral drug development.
The ability of a virus to recognize its environment, including the substances it produces Host“It’s another complication to the virus-host interaction,” adds Evan Ariel, a professor of biological sciences and senior author on the new paper. Nowadays, viruses are using that ability to their advantage. But in the future, he said, “we can use it to hurt them.”
Not by chance
The new research focuses on bacteriophages – viruses that attack bacteria, as they are often simply called.phages“The levels in the study could infect their hosts in 2018 Bacterial cells Bacteria have special appendages called pili and flagella that help them move and attach. The bacteria produce a protein called CtrA that controls the production of these additives. The new paper shows that many attachment-dependent phages have motifs in DNA that the CtrA protein can bind to. which has a phage Mandatory position Because the protein produced by the host is abnormal, says Ariel.
More interestingly, Ariel and the paper’s first author, Elia Mascolo, Ph.D. student in Ariel’s lab, found through detailed genomic analysis that these binding sites are not specific to a single phage, or even a single group of phages. Many different phage species have CtrA binding sites—but all require pili and/or flagella to infect their hosts. It can’t be a coincidence, they decided.
The ability to control CtrA levels has evolved over time in different phages that infect different bacteria, Erill says. When it is far away Related species Show the same behavior, it is called Coordinated evolution– and the feature is definitely useful.
Timing is everything.
Another wrinkle in the story: the first Phage The research team found that CtrA binding sites attack a group of bacteria called Caulobacterales. The Caulobacterales are a particularly well-studied group of bacteria, because they exist in two forms: a free-swimming “swarmer” form and a surface-bound “clumped” form. The filaments have pili/flagella, and the filaments do not. In these bacteria, CtrA is also regulated Cell cycleA cell divides equally into two more identical cell types or divides asymmetrically to form one stem cell and one stem cell.
Because the phages can only infect the jaw. Cells, it is best to leave the host when there are too many malicious cells to infect. In general, Caulobacterales live in nutrient-poor environments, and they are very widespread. “But when they find a good pocket of microhabitat, they become suspended cells and multiply,” says Ariel, eventually producing large amounts of jaw cells.
So, “we hypothesize that the phages are monitoring the levels of cTra going up and down through the cell’s life cycle, when a cancer cell is becoming a straw cell and a factory for invaders,” says Ariel. At that time they blew up the cell. This is because there may be more flocks nearby to pollinate.
Unfortunately, the method of proving this hypothesis is labor-intensive and extremely difficult, so that was not part of this latest paper—though Erill and his colleagues hope to address that question in the future. However, the research team sees no other plausible explanation for the proliferation of CtrA binding sites in different phages, all of which require pili/flagella to infect their hosts. Even more exciting, they state, are the implications of viruses infecting other organisms and even humans.
“Everything we know about phages, every single evolutionary strategy has been translated into viruses that attack plants and animals,” he said. “It’s almost a given. So if phages are listening to their hosts, viruses that infect humans are likely to do the same.”
There are quite a few. Other examples of documents Phages control their environment in interesting ways, but none of them include many that employ the same strategy to challenge many different bacterial hosts.
According to Ariel, this new research “is the first broad demonstration of what is happening in the cell, in this case, in terms of cell growth, where we listen to phages.” But more examples are on the way, he predicts. Members of his lab are beginning to look for receptors for other bacterial regulatory molecules in phages, he said.
New ways of treatment
The main takeaway from this study is that “the virus is using cellular intelligence to make decisions,” says Ariel.
For example, to optimize strategies for survival and replication, an animal may want to know what tissue the virus is in or how strong the host’s immune response is. While it’s unsettling to think about the information that viruses can collect and possibly make us sick, these discoveries open the way to new treatments.
“If you are making an antiviral drug and you know that the virus is responding to a different signal, you may be fooled. Virus“Eril says. But this is still many steps away. But for now, we are beginning to realize how actively we are. Viruses Have an eye for how they observe what’s around them and make decisions based on that. “It’s fun,” he says.
Elia Mascolo et al., The transcriptional regulator CtrA regulates gene expression in alphaproteobacterial phages: evidence for a lytic delay pathway; Frontiers in Microbiology (2022) DOI: 10.3389/fmicb.2022.918015
University of Maryland Baltimore County
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