It’s kind of a nature freak. This is what scientists initially thought when they discovered a virus with a genome that had a different structure from other living things on Earth nearly 50 years ago. So they began to look for other such whims, but did not find any of them, and they stopped looking. Even now, when the whole world started to care about viruses due to the SARS-CoV-2 pandemic.
The influences of the work of three research teams have been published in the prestigious journal Science. They show that there is an army of atypical viruses. Scientists have also discovered how it is formed, but research continues. More work is expected to lead to the development of new treatments for some diseases, such as gastrointestinal diseases and bacterial infections. Perhaps they will also help answer the question of why these strange viruses developed. Is it just to get better protection against the bacteria attacking them, or are they aliens who started life on Earth?
The plant, the frog and the man
Scientists have discovered an unusual genome structure in some phages, a group of viruses that have been waging war against bacteria for millions of years. They penetrate inside and destroy them. But bacteria are constantly changing to avoid a deadly attack. So if viruses want to defeat bacteria, they must also evolve. One such approach was to alter the structure of a small portion of the genome.
So how does this atypical DNA of some phages differ from other organisms? The genetic material of nearly every living organism on our planet, from plants to frogs to humans, is made up of four nucleotides, denoted by the letters ATCG. However, some phages, called phages for short, do not have an A nucleotide in their genome, but others – marked with the letter Z – explains Dr. Elbieta Lenartowicz, Head of the Molecular Diagnostics Laboratory at the Institute of Organic Biochemistry in Poland, Academy of Sciences in Poznan . Scientists say that such a virus is a virus with a Z genome.
Scientists discovered the first such virus, Cyanophage S-2L, which attacks cyanobacteria, in 1977. In the late 1980s, they showed that the Z nucleotide is very stable at high temperatures. It binds more strongly to the elements in the DNA strand and is more resistant to some of the proteins in bacteria that would normally destroy viral DNA. When the ZTCG virus penetrates inside the bacteria, the enzyme is not fully aware that it is an enemy. Thanks to this virus, it is easier to replicate and destroy in a bacterial cell compared to a virus with the ATCG genome structure – Dr. Lenartowicz explains.
In the latest study, scientists from the Pasteur Institute in France and Shanghai Technical University describe how a Z nucleotide is formed and how it is incorporated into the genome of bacteria. They found it in more than two hundred different types of viruses. In future studies, they plan to find out what happens when the Z genome is incorporated into cells that previously did not contain it. Perhaps this will create a new tool for gene therapies. And since the virus is effective at destroying bacteria thanks to the Z nucleotide, it may be possible to use it to treat bacterial infections. Scientists are already using phages to treat some bacterial infections, but using phages together with the Z genome could make such treatments more effective.
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Visitors from outer space
In addition to the practical application of the latest discoveries, scientists also want to clarify when Z viruses evolved and under what conditions they occurred. One hypothesis is that the first viruses containing Z nucleotides appeared on Earth, and thanks to this genome structure, they were able to survive in hot and hostile conditions in the early existence of our planet. Only from them evolved viruses and organisms with the genetic material ATCG. Another theory is that Z nucleotides came here from space and gave rise to life on Earth.
Scientists in the nineteenth century have already talked about the origin of life outside planet Earth. Research from the second half of the twentieth century onwards showed that many of the chemical compounds essential to life on Earth, including the building blocks of DNA, formed in interstellar space and were brought on by meteorites that bombed Earth billions of years ago.
This theory was confirmed, for example, by searching for the famous carbon meteorite Murchison, which fell to Earth on September 28, 1969 near the town of Murchison in the state of Victoria in South Australia. In the parts of the rocks made of the interstellar raw material that make up the solar system, scientists have found more than 70 amino acids, the chemicals from which proteins are made. Only 19 of them are known on Earth. Spectroscopic analyzes showed that there could be thousands of different organic materials within rock fragments, including the bases needed to form the Z-nucleotide.
Michael Groom and Farren Isaacs of Yale University proposed another theory for the formation of Z genomes. In their opinion, the genetic material created in this way was present alongside typical DNA at the beginning of the formation of life on our planet, 3.5 billion years ago. Analysis of a meteorite that fell on Australia in 1969, conducted in 2011, indicates that the Z-nucleotide is likely to have an extraterrestrial origin. So it could play a major role in the emergence of the earliest life forms on Earth, ” the researchers wrote in the journal Science.
Marriage of bacteria and viruses
Scientists have been interested in phages for a long time. In 1919, doctors in Europe, and especially in Germany and the USSR, suggested their use in patients with various bacterial infections. Research on these viruses has also been initiated by a center operating at the Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences in Wroclaw. In the second half of the twentieth century, virotherapy lost its relevance as antibiotics became increasingly used to fight bacteria. Scientists became interested in it again several years ago, when it became known just how serious a public health problem is the resistance of bacteria to antibiotics.
It was recently discovered that phages can attack bacteria in two main ways. The first mechanism is for viruses to enter cells and control the mechanism of protein production. This allows them to multiply, and the newly formed virus particles infect more and more bacteria. In the second mechanism, the viral genome is incorporated into the bacterium chromosome. They remain dormant for many generations of bacteria until favorable changes occur in the environment. The virus then liberates itself from the host’s chromosome, and begins proliferating and infecting new cells.
The ability of phages to incorporate their genomes into the bacterium chromosome has been of interest to Jose Benadis of Imperial College London for several years. The scientist believes that these viruses drive the development of bacteria. He and his team describe different ways of exchanging genetic material between bacteria that phages help. These results help understand not only how viruses replicate in infected cells, but also how bacteria exchange genes.
Hence the idea of new treatments – phages can be directed to convert pathogenic bacteria into harmless bacteria. The first experiments were carried out last year by scientists from the universities of Wuhan and Beijing. They used Siphoviridae to fight Bordetella bronchiseptica, which often causes respiratory illnesses in cattle. They found that the bacterial cells infected with the virus were less virulent than the other cells. It is possible that the viral genome has penetrated into the gene that the bacteria need to infect the host. In another experiment, the researchers showed that phages could act as a vaccine – mice that had been injected with viruses prophylactically were protected from Bordetella infection.
The bacteria can also interact with the immune system. This was demonstrated in studies on mice by the University of Utah microbiologist on the June tour. Other experiments were carried out by Dr. Pauline Scanlan of the University of Oxford. I studied Pseudomonas fluorescens, a bacterium in the wild that is harmless to humans but sometimes evolves – it secretes large amounts of a compound called alginate that surrounds the cell with a protective sticky substance. This coat protects the bacteria from attack by the host’s immune system and makes them resistant to the action of antibiotics. The scientist showed that bacteria covered with a mucous layer are also more resistant to bacterial infection than normal cells.
Power is in the microbiome
Our health condition may depend on the bacteriophages in the intestine. These viruses influence bacterial formation in the mammalian microbiome. In 2019, scientists at Harvard Medical School showed in animal studies that phages not only directly affect the bacteria in the gut of mice, but also affect the rest of the microbiome by altering their chemical and biological makeup.
An interesting experiment was performed a few years ago by microbiologists Brick Doorkop and Laura Hopper of the University of Texas Southwestern Medical Center in Dallas. Researchers studied Enterococcus faecalis, which lives in the human intestine and is usually harmless, but can become dangerous pathogens under favorable conditions. They were given to mice a strain of E. faecalis that is resistant to many antibiotics and that causes infection, sometimes life-threatening, in hospitalized patients. They noticed that some of the genes in E. faecalis did not come from the bacterial genome, but from the phage genome. These genes were incorporated into the genetic material of the bacteria and kept dormant by many generations of the bacteria. It only became active when the bacteria started threatening the life of the mice. It’s as if they want to help their host and balance the gut microbiome.
Scientists are just beginning to understand the importance of phages for the microbiome in our gut. They began research to clarify the link between these viruses and human diseases. They have already shown that patients with Crohn’s disease and ulcerative colitis have elevated levels of some phages, especially Caudovirales. Other researchers believe that changes in bacterial makeup promote diabetes and some types of cancer. All this is due to the disruption of the microbiome caused by the phages. Strange viruses that may have come to us from space.
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