Stories about bacteriophages were discovered and spread from the Ganges River in India, and some even see them as a savior against the coronavirus, but what is the truth? Today I will share with you the knowledge about bacteriophages.
Press photos
In 1896, the British bacteriologist Ernest Hankin discovered that Indians used to throw corpses into the river in the Ganges, but the cholera epidemic in India was more moderate than anywhere in Europe, and he believed that there were substances in the water that killed germs. More than 20 years later, British bacteriologist Frederick Twort and French microbiologist Félix d'Hérelle independently discovered a tiny substance that could kill bacteria. d'Hérelle named this type of virus bacteriophage, or bacteriophage.
Ganges, India
In 2016, an American was unfortunately infected with the Iraqi bacteria known as the world's six super bacteria, which is said to have been infected after visiting the Egyptian pyramids. When he tried all the antibiotics to no avail, the doctor injected phages into him and successfully killed the bacteria in the body, so that he was recovered.
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Superbugs
Bacteriophage is a general term for viruses that infect cytoform microorganisms such as fungi, bacteria, actinomycetes and other cells, and is widely distributed in nature. According to the relationship between phages and host bacteria, it can be divided into two categories: strong bacteriophages and mild bacteriophages.
Bacteriophage 3D renderings
Virulent phage: Infects host cells and replicates normally within the cells and eventually kills the cells, forming a lytic cycle.
Mild bacteriophage or lysogenic phage: The replication cycle cannot be completed after infection with the host cell, and the phage genome exists in the host cell for a long time without mature phage production.
One-step growth curve of potent bacteriophages
。 The incubation period varies from virus to virus, with phages in minutes and animal and plant viruses in hours or days.
During the first stage of the incubation period, the infected virus is not detected in the infected cells, and in the latter stage, the number of infectious viruses in the infected cells increases sharply. The time from the time the virus disappears within the infected cell to the time when a new infectious virus appears in the cell is a period of concealment.
, thus proving that the offspring virus particles are matured by the assembly of newly synthesized viral genomes and proteins, rather than by double splitting.
Lysis period: After the completion of the assembly of the offspring phage, the host cells will be lysed to form new plaques, at which time the number of plaques will rise linearly, which is the lysis phase.
Lysis renderings of potent bacteriophages
Renderings of mild bacteriophage infestation
A characteristic of mild phages that do not produce progeny phages immediately after invading host cells is called lysogenicity. After a mild phage infects a host cell, its DNA is integrated into the host chromosomal DNA, which is in an integrated state of phage DNA called a prephage. The prophage is evenly distributed into the daughter cells as the host cells divide, which is due to the fact that the genetic information of the prophage is temporarily unable to be expressed by the action of the specific repressors it encodes.
The phage "cocktail" formulation made by the Eliava Institute of the former Soviet Union contains a combination of several phages to broaden the antibacterial spectrum and/or improve the bactericidal effect against a certain pathogenic bacteria, and the graduate student still exists and continues to conduct relevant research. In recent years, with the increasing threat of high-level drug-resistant pathogenic bacteria, more researchers have re-invested in the study of bacteriophage therapy, and the United States, the United Kingdom, Germany and other countries have carried out a large number of experiments and achieved good results.
(1) Clinical use of bacteriophage preparations
As a microbial virus, bacteriophages have natural lysis ability and innate adaptability advantages to bacteria, and current antibacterial drugs are not easy to break through the blood-brain barrier into brain tissue, therefore, bacteriophage therapy has become an alternative alternative to antibiotics, and the current clinical application of phage therapy mainly includes the following 5 kinds:
Blood-brain barrier
1. Systemic application of treatment, the route of administration of bacteriophages is mainly oral and intravenous, and there is still no recognized standard in terms of dosage.
2. Topical application therapy, its effect is similar to antibiotics, mainly applied to local infections, the experimental study effect of the method shows that there is still a certain effect on vascular-related skin ulcers and other diseases when antibiotics are ineffective.
3. Inhalation therapy for lung infection, this method also belongs to the local treatment, the bacteriophage system that can be applied to inhalation therapy is mainly divided into two categories: liquid preparations (including suspension preparations, liposome encapsulation preparations) and solid preparations (inhaled dry powder preparations), but the potency and stability of the preparations, the way of inhalation, etc. still need to be further improved by basic and clinical research.
4. Bacteriophage lyase treatment, in the process of lytic phage infection bacteria, there are 2 kinds of lyases, namely virus-related peptidoglycan hydrolases and bacteriophage in vivo lysin, the current clinical research application of lysozymes are mostly endolysin, some preparations have been used clinically, adverse reactions are mild.
5. The combination of phages and antibiotics, the mechanism of phage sterilization is completely different from that of traditional antibiotics, which also means that the combined application of phages and antibiotics may theoretically have a synergistic effect. Judging from the current reports, some combination therapies have significant synergistic effects, and the specific efficacy needs to be supported by more experimental data.
Combination therapy
Bacteriophage therapy has its own particularity, and its treatment advantages are obvious, mainly manifested in five aspects. But bacteriophages are clearly not omnipotent, and some people even see phages as saviors to save the new crown epidemic, which obviously exaggerates the effect of bacteriophages. For example
Although bacteriophage therapy has a history of more than 100 years, more scientific researchers are still needed to continue to work hard to make new breakthroughs in order to be widely used in clinical practice.
There are many more research on bacteriophages, this article is only a selection of some of them to share with you, welcome to leave a message to discuss.
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bibliography:
WANG Rentao, LIU Youning. Clinical application and progress of phages in the treatment of bacterial infections[J]. Chinese Journal of Tuberculosis and Respiratory Disease, 2020, 43(06):539-543.
ZOU Xiuyue, CAI Dezhou. Research Progress and Development Direction of Bacteriophages in the Treatment of Bacterial Diseases[J]. Chinese Journal of Infection Control, 2019.18(9):888-892.