Is there really no way to deal with antibiotic resistance? Future antidotes to "superbugs" →

Pathogenic microorganisms that cause illness exist in every aspect of our lives, and we are exposed to the risk of bacterial infection all the time. Is there an organism that also scares bacteria and plays a role in counteracting bacteria in nature?

Today, we will share with you a magical virus in the ecological world - bacteriophage .

1 What is a bacteriophage?

Bacteriophages are viruses that can infect and invade microorganisms such as bacteria, fungi, and actinomycetes. Their name comes from the Greek word " phagos ", which means "to devour", and is mainly named for their ability to lyse host bacteria [1-2]. Although people are not familiar with them, they are more common around us than bacteria. They are abundant and diverse biological entities on Earth, with an estimated number of 1031, which is about 10 times more than bacteria. They control the number of bacteria and evolve with them [3].

Bacteriophages were discovered in 1915, 13 years earlier than the currently widely used antibiotics. However, due to the First World War at the time, research on bacteriophages, which were cumbersome to cultivate and had a narrow host spectrum, was put on hold. In 1928, the first antibiotic, penicillin, was introduced.

Penicillin’s amazing therapeutic effect completely outperformed bacteriophages, causing most scientists to shift their focus to the development of more effective antibiotics [4]. However, a small number of scientists still persist in exploring the basic properties of bacteriophages and disease treatment. They have been quietly studying them for a hundred years, laying a solid foundation for the use of bacteriophages as an alternative treatment for drug-resistant bacterial infections today.

In recent years, due to the abuse of antibiotics, the slow progress in the development of new antibiotics, and the rapid increase in the number and types of drug-resistant bacteria, scientists have come up with the long-dormant phage therapy in order to find solutions and better treat patients.

2 How bacteriophages work

Phages have high specificity, in other words, a phage can only attack a limited range of bacteria (the type of bacteria or its variants). There are two categories of phages, virulent phages and temperate phages, and their attitudes towards bacteria are just like their names, one is "fierce" and the other is "gentle".

After identifying the bacterial surface antigens that match them, the phage attaches to the surface and uses the tail spines under its tail to pierce the bacterial shell. It then squeezes its tail to inject its own DNA or RNA into the bacteria. The virulent phage uses the nutrients of the bacteria to quickly replicate genetic material and assemble new phages. The temperate phage is not in a hurry to replicate. It first integrates its own gene sequence into the bacterial chromosome, and then divides with the bacteria, passing it down from generation to generation. When necessary, it restarts its lysis ability, rapidly reproduces and assembles. The bacteria eventually lyse and die due to excessive internal pressure, releasing the phage. The newly released phage immediately looks for new targets and repeats the above steps to kill the pathogenic bacteria. The phages currently used in phage therapy are mainly virulent phages.

3 Characteristics of bacteriophages

Bacteriophages have high specificity and diversity:

As mentioned earlier, a bacteriophage can basically only attack a limited range of bacteria (that type of bacteria or its variants). Bacteriophages are abundant in nature, and bacteriophages with different recognition ranges also come in various shapes and sizes.

Bacteriophages are highly effective:

Bacteriophages have strong replication and proliferation capabilities. They multiply at an exponential rate in the infected area and can quickly (within 24 hours) effectively eliminate pathogens.

Bacteriophages have good biosafety:

Bacteriophages are insensitive to other non-specific bacteria and will not destroy other bacterial flora. At the same time, because bacteriophages are self-limiting and cannot survive outside the bacterial host, once the host disappears, the bacteriophages will degrade and be excreted from the body and will not remain in the body[5].

4 Application of bacteriophage

Phage therapy has gradually entered our lives. As the problem of antibiotic resistance continues to worsen, phages have made breakthroughs in multiple diseases caused by bacterial infections as an alternative therapy for drug-resistant bacterial infections. The main directions of phage therapy are currently whole phage therapy and lytic enzyme preparation therapy.

Scientists use the high specificity of phages to mix a variety of phages with different antibacterial spectra to make a "cocktail preparation". This treatment is called " cocktail therapy " and is a common method in full phage therapy. In order to improve the bactericidal effect, there is now also a method of using phages and antibiotics in combination for treatment.

The medical phage products currently developed cover diseases caused by a variety of bacteria , such as purulent inflammation caused by Staphylococcus aureus, typhoid fever, acute gastroenteritis or sepsis caused by Salmonella typhi and Salmonella paratyphi, bacterial dysentery caused by Shigella, infectious diseases caused by Listeria and Klebsiella, as well as enterocolitis, acute and chronic colitis, dysbacteriosis, and infectious inflammation of the ears, nose and throat caused by other pathogenic bacteria.

Diseases that bacteriophages are involved in preventing include streptococcal diseases, Escherichia coli diseases and other gastrointestinal diseases, clearing possible colonizing bacteria during organ transplantation, increasing the success rate of organ transplantation, and adjusting the flora of multiple epidermal sites to prevent bacterial infections [6].

5 Bacteriophages may be the antidote to "super bacteria"

"Super bacteria" refers to multidrug-resistant bacteria that are resistant to almost all antibiotics and thus escape death. Once we are infected with such bacteria, it is difficult to cure them, and there was once no cure, posing a great threat to our health.

Scientists usually have only two ways to solve this problem: one is to continue to develop new antibiotics to fight against them, and successfully develop alternatives before super bacteria develop new drug resistance; the other is to find another way and use phage therapy to kill them by surprise without phage resistance.

Nowadays, the development of antibiotics has entered a bottleneck period and the development speed is slow. It is particularly difficult to use new antibiotics to alleviate the pressure brought by super bacteria. Bacteriophages may be the antidote for super bacteria and at the same time bring hope of life to patients with severe multidrug-resistant bacterial infections.

The narrow host spectrum of bacteriophages makes it possible to select specific pathogens and avoid normal flora. This ensures treatment without causing harm to patients. It solves the problem of antibiotics that indiscriminately attack pathogens and normal flora, and provides a new idea for preventing problems similar to those caused by antibiotics that harm the human body itself.

The era of bacteriophages has arrived. Let us look forward to its inclusion in daily medical care and jointly fight against the invasion of pathogenic bacteria.

The popular science theme of this article is derived from the TOP10 hot frontiers in the field of biological sciences in the "Research Frontiers 2024" report

【References】

[1] Cong Cong, Li Jibin, Wang Lili, et al. Study on the early historical documents of bacteriophages in China[J]. Foreign Medicine (Antibiotics), 2023,44(2):73-82.

[2] Dion MRB, Oechslin F, Moineau S. Phage diversity, genomics and phylogeny[J]. NATURE REVIEWS MICROBIOLOGY, 2020,18:125.

[3] Salmond GPC, Fineran P C. A century of the phage: past, present and future[J]. Nature Reviews Microbiology, 2015,13(12):777-786.

[4] Hong Ruoxuan. Review of research progress in phage therapy for bacterial infections[J]. Modern Business and Industry, 2019(13):71-74.

[5] Zhang Zhihong, Zhong Youhong, Wang Peng. Research status of phage therapy[J]. Chinese Journal of Tropical Medicine, 2021, 21(7): 698-703.

Editor: Liu Yang and Zhao Na

Proofread by Li Na and Li Yule

Producer: Peng Bin

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