Writing a virus seems to have lost in the beginning, compared to other more macroscopic species.
Compared with the long history of biological evolution, the history of human civilization and naturalist studies is too short, and the phage is a special kind of virus that is invisible to the naked eye and optical microscope. It is not until the electron microscope appears that we can get a glimpse of humanity.
We cannot find any literary works to praise its fine morphological structure or ingenious breeding mechanism, and there is no great historical person to leave the anecdote of the relevant anecdotes. To date, We still don’t know where it originated and where it was born . They are just as faithful companions of human Research in molecular biology and medicine, and are silently present in every corner of the world.
Heng’s mysterious “creature”
Back in 1896, British bacteriology Ernest Hanbury Hankin, who studied cholera in India, stumbled upon the presence of a substance in a boiling river water that inhibits the growth of Vibrio cholerae, limiting the spread of cholera. Subsequent studies have found that the substance is very small, and that the is tiny to a bacterial filter that can be made from ceramic (with holes that cannot be passed by bacteria).
More than 20 years later, British bacteriology Frederick Twort and French microbiologist Félix D ‘ Hérelle independently found a tiny substance that could kill bacteria. Twort that the substance may be derived from a particular bacterial growth cycle, and that the may be an enzyme secreted by the bacterium itself , or a virus that infects bacteria. Unfortunately, the outbreak of World War I caused him to interrupt the study.
On the other side, d ‘ Hérelle is convinced that eating his dysentery Shigella culture is a parasitic virus . According to Greek φαγεῖν (Phagein), he named the virus bacteriophage, the phage.
Now we know that phage is a class of viruses that can infect bacteria and archaea , which is composed of protein and nucleic acid . According to the morphological structure and the different types of nucleic acid can be divided into 19 families.
Unlike other types of organisms, the naming of viruses does not follow the two-name method : The naming of plants and animal viruses generally follows the form ” host main + virus “. For example, Tobacco mosaic virus (Tobacco mosaic virus,tmv) and canine parvovirus (canine PARVOVIRUS,CPV), and phages generally ” host host bacterium name + phage + number ” To name the form, such as the Enterococci phage T4 (Enterobacteria phage T4).
The 1940s, American geneticist Milislav Demerec isolated a series of phages from sewage samples from sewers, and based on host and plaque [ [ 1] size , naming them as phage t1~t7.
The enterovirus phage T4 is subordinate to the muscular tail phage Division (Myoviridae), according to which we know that T4 can be infected with the intestinal bacillus (Enterobacteriaceae) of the Escherichia coli (Escherichia coli).
Note 1: Plaque-plaque produced by bacterial death on the culture medium.
In Buddhist terms, the term ” Heng ” is a metaphor for the difficulty of counting, which may well be used to describe the phages first found in the Ganges. Currently, the phage is the most numerous species on Earth [Note 2], which exists almost anywhere on earth where there are bacteria, and 70% of bacteria in seawater contain phages.
Note 2: The nature of phage is virus. The virus is very special, not strictly a “creature”, which has the same genetic material (DNA or RNA) as the general life form, can proliferate and evolve through natural selection, but without the cellular structure, which is an important reason that it is excluded from the “Life Body”. At present, the virus is described as being dissociated from the “organism boundary” (organisms at the edge of life).
Is it a creature or a nano robot?
Under the electron microscope, the T4 is a tadpole-shaped , about 90 nm wide and 200 nm long, consisting of an ellipsoidal head and a cylindrical tail . People’s further analysis of its morphological structure and multiplication way makes T4 a strong sci-fi sense.
T4 ‘s head, also known as the capsid , is an elongated 20-face body, consisting of 152 protein capsid grains, which cover a section of a 289-protein-encoded double strand of DNA. Neck link between head and tail. The tail is a hollow tubular structure consisting of 6 spines and 6 tail filaments connected with the tail tube and the outsourced tail sheath, the base plate at the bottom, and the substrate.
T4 phage morphological structure and infection pattern. Picture: guido4/wikipedia.org: Species Calendar
The process of T4 infection with Escherichia coli is similar to a miniature syringe : The protein on the tail wire identifies and binds the lipopolysaccharide receptor on the host cell, the tail sheath shrinks, the tail tube pierces the outer layer of the bacterial cell wall, and the cell wall is degraded by the action of Lysozyme, The DNA of the head can be easily injected into the bacterium by the tail tube.
The DNA then begins to transcribe RNA, translating it into protein, and mass production of self-replicating essential components for assembly : The empty capsid is first wrapped in DNA, combined with a assembled tail, and finally connected to the tail wire. In this way, a healthy Escherichia coli cell is hijacked into a T4 ” assembly Plant “, in the role of Lysozyme and lipase, the assembly plant wall eventually collapsed, the released phage will continue to search for the next victim.
It is still not possible to confirm when and where the phage evolved. Their ingenious structure and efficient process of infection and multiplication make many people sigh that this is not like the earth life, but some alien civilization left the ” Nano robot .” As a result, T4 has also become a frequent guest in many works of art and science fiction: in the first season of the animated “Rick and Morty”, there was an outbreak of E. coli, although the image of “E. coli” in the film was actually a distorted phage.
T4 is simple in structure and easy to be cultured in the laboratory and harmless to human body, so it is often used as a model species in molecular biology and virology experiments. Many Nobel Prize winners in Physiology or Medicine have used T4 as a research model , such as the 1969 winners Max Delbrück, Salvador Luria and Alfred Hershey, who were awarded the prize for discovering the virus’s replication mechanism and genetic structure.
Three Nobel Prize winners in Physiology or Medicine in 1969. Picture: nobelprize.org
Phage therapy
If you pay attention to science news, you may know that antibiotics are no longer available to fight against many drug-resistant ” Super Bacteria “. Currently, researchers are trying to use the “new” method of phage therapy to control infection, and many phage products have entered clinical trials.
In fact, phage therapy is nothing new, as early as 1919, the phage-Félix d ‘ Hérelle has used a phage isolated from chicken feces to kill salmonella and cured the chicken population of typhoid; in August, he successfully cured two children with dysentery from a phage isolated from the feces of a recovering dysentery patient.
In the the 1940s, antibiotics, led by penicillin, began to be mass-produced and commercially, allowing phage therapy to be forgotten, and only a handful of countries dominated by the Soviet Union still adhere to the research and application of phage therapy. During World War II, phages were used to treat the diarrhea, typhoid and gangrene of Soviet soldiers.
Due to the lack of antibiotics, the newly established China has also developed a phage preparation with the help of the Soviet Union, and successfully cured dysentery and Pseudomonas aeruginosa infection cases. According to the real event adaptation of themovie “Spring full of the world”, it is narrated the use of phage treatment of burns patients infected with the story.
Since then, there have been “superbugs” that tolerate almost all antibiotics because of antibiotic abuse. In the face of the drug-free dilemma, phage therapy has returned to people’s eyes. The advantage of phage therapy, compared to antibiotics, is specificity : Once a suitable phage virus is found, the only hits the target pathogen in , and Antibiotics can also kill both the beneficial and harmful bacteria in the same environment . For example, the protagonist of this article T4 only to eliminate E. coli, there have been studies to T4 and T5 to control the intestinal tract of the sheep infected with hemorrhagic Escherichia coli O157:h7 strains.
Hemorrhagic Escherichia coli O157:h7 culture. Most Escherichia coli is not pathogenic, only a few strains such as o157:h7 can cause intestinal infections. Picture:foodsafetycertification.ca
However, there is no flaw in phage therapy, and the narrow host lineage is both an advantage and a weakness, and a phage strain often kills only certain strains of a bacterium, so finding a corresponding phage to fight against the pathogen is a challenge. In the face of complex infections, researchers often adopt the “cocktail preparation” approach, where mixes multiple phages to extend the host lineage . In addition, as an external material to introduce the human body, phages may also stimulate some people’s immune response, causing allergic reactions and other side effects .
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