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Scientists have discovered how a common virus in the human gut infects and takes over bacterial cells, a discovery that could be used to control the composition of the gut microbiome, which is important for human health.
Rutgers co-authored research, which could help efforts to design beneficial bacteria that make medicines and fuels and clean up pollutants, was published in the journal Nature.
“CrAssphages are the most abundant viruses that infect bacteria in the human gut. As such, they likely control our gut community of microbes (the microbiome),” said co-author Konstantin Severinov, principal investigator at the Waksman Institute of Microbiology and professor of molecular biology and biochemistry at the Rutgers University-New Brunswick School of Arts and Sciences. “Understanding how these tiny viruses infect bacteria can allow scientists to control and manipulate the composition of the microbiome, increasing the percentage of beneficial bacteria in our gut or decreasing the number of harmful bacteria, thereby promoting health and fighting disease.”
Scientists have discovered that crAssphages use their own enzyme (an RNA polymerase) to make RNA copies of their genes. RNA possesses the genetic information to make proteins. All cells, from bacterial to human, use these enzymes to make RNA copies of their genes. And these enzymes are very similar throughout living matter, which implies that they are ancient and related by common ancestors, Severinov said.
When the team revealed the atomic structure of a crAssphage enzyme, they were surprised to learn that it is distinct from other RNA polymerases but closely resembles an enzyme in humans and other higher organisms involved in RNA interference. Such interference silences the function of some genes and can lead to certain diseases.
“This is a surprising result. It suggests that RNA-interfering enzymes, a process thought to occur only in the cells of higher organisms, were ‘borrowed’ from an ancestral bacterial virus early in evolution.” , Severinov said. “The result provides a glimpse of how the cells of higher organisms evolved by mixing and matching simpler cell components and even their viruses.”
“In addition to profound evolutionary insights, phage (viral) enzymes such as crAssphage RNA polymerase can be used in synthetic biology to generate genetic circuits that do not exist in nature,” he said.
According to the National Human Genome Research Institute, synthetic biology involves redesigning organisms so that they can, for example, make a medicine, nutrient or fuel, sense something in the environment, or clean up pollutants.
“We’re now trying to match the thousands of different crAssphage viruses in our gut with the bacterial hosts they infect,” Severinov said. “By using only the” right “bacterial virus, we will be able to get rid of the bacteria it infects, which will allow us to alter the composition of the gut microbiome in a targeted way.”
Leonid Minakhin of the Waksman Institute of Microbiology contributed to the study along with scientists from many other institutions.
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