Phage therapy: precise attack on soil-borne pathogens is expected to replace chemical pesticides and antibiotics
◎Our reporter Jin Feng
The method of using phages to control pathogenic bacteria is called "phage therapy", which is a green ecological technology that is expected to replace antibiotics.
At present, domestic research units have collected a large number of phage resources for different plant diseases, studied the mechanism of action of different phages, and the interaction between phages, and used different phages to jointly inhibit soil pathogenic bacteria.
Phages are a type of virus that specifically "eat" bacteria, and they are widely found in marine and terrestrial natural ecosystems.
By infecting host bacteria, phages can regulate the number of bacterial populations, drive changes in the diversity and composition of bacterial communities, and then affect ecosystem functions.
However, for a long time, the relationship between bacteriophages in soil and crop soil-borne diseases has been rarely studied.
Recently, the international academic journal "Microbiome" published online the latest research paper of Shen Qirong's team, academician of the Chinese Academy of Engineering and professor of the School of Resources and Environmental Sciences of Nanjing Agricultural University.
The team found that the occurrence of soil-borne bacterial wilt is closely related to the composition of the crop rhizosphere phage community and the interaction characteristics of phage-host bacteria.
This study is the first to demonstrate the potential impact of phages that specifically infect indigenous bacteria on the invasion of soil-borne pathogenic bacteria R. solanacearum, and provides a new theoretical basis for using phages to reduce crop soil-borne bacterial wilt caused by R. solanacearum.
Targeted elimination of pathogenic bacteria, more friendly to the environment
In agricultural production, chemical pesticides and antibiotics have been widely used, but unreasonable use will cause soil function degradation, environmental pollution and other problems.
"For example, the indiscriminate use of chemical pesticides can significantly increase the resistance of pathogenic bacteria and the risk transmission of resistance genes. In addition, there are also a large number of indigenous microorganisms in hotspots where pathogenic bacteria interact with their host plants. It plays an important role in resisting the invasion of pathogenic bacteria and infecting host plants. However, broad-spectrum bactericidal antibiotics and chemical pesticides will also destabilize the structure and function of indigenous microbial communities in soil while inhibiting pathogenic bacteria.” Shen Qirong It is introduced that in order to protect the health of soil, animals and plants, and the environment, new measures that effectively target and eliminate soil-borne pathogenic bacteria and are environmentally friendly are urgently needed.
Bacteriophages are the "chosen ones" among them.
Phage is a type of virus that specifically infects bacteria and is ubiquitous in the environment. "Currently, the number of phages in the earth's biosphere is as high as 10^31. The method of using phages to block and control pathogenic bacteria is called 'phage therapy'. A green ecological technology that is expected to replace antibiotics." Wei Zhong, a co-corresponding author of the paper and a professor at Nanjing Agricultural University, told the reporter of Science and Technology Daily.
At present, phage therapy has been widely used in clinical medicine, animal husbandry, aquaculture and planting and other fields.
Wei Zhong introduced that phage therapy has several advantages: phage can recognize specific pathogenic bacteria and has little impact on the environment; phage can use the host to proliferate and enter the bacteria to efficiently lyse pathogenic bacteria; the application of phage therapy can reduce the use of antibiotics, Provide guarantee for food safety.
Create a phage "cocktail" to protect plant health
"Phage therapy had already been applied before antibiotics were popularized." What Wei Zhong said was true.
Since the discovery of phages, phage therapy has been continuously developed, and there have been many attempts to solve crop health problems caused by pathogenic bacterial infection.
In 1924, researchers discovered that phage-like substances in cabbage filtrate prevented cabbage rotting caused by Xanthomonas bacteria.
Subsequently, the substance was widely used in the prevention and treatment of solanaceous crop bacterial wilt, kiwifruit bacterial canker, and fruit tree fire blight caused by Ralstonia solanacearum, Erwinia, Pseudomonas syringae, and Xanthomonas campestris. , citrus spot, rice leaf blight, potato onion soft rot and black shank, etc.
In 2005, the U.S. Environmental Protection Agency approved for the first time phage products to control bacterial spot of tomato and pepper caused by Xanthomonas campestris and Pseudomonas syringae.
In 2011, the U.S. Environmental Protection Agency approved a company's bacteriophage biopesticide for the control of tomato canker.
At present, domestic research institutes have collected a large number of phage resources for different plant diseases, and these phages provide resource guarantee for effective disease prevention and control.
Shen Qirong's research team aimed at R. solanacearum.
Ralstonia solanacearum can cause wilting of important economic plants such as tobacco, potato, tomato and ginger by infecting the roots of crops in the soil.
In severe cases, it can lead to large-scale crop yield reduction or even failure.
"The obligate phages of R. solanacearum feed on R. solanacearum. They can enter the R. solanacearum body, proliferate in large quantities, and finally crack and kill R. solanacearum. There are also many indigenous bacteria in the soil, and these bacteria also have their own 'Exclusive' phage. When R. solanacearum is inhibited by its obligate phage, other bacteria in the soil will 'take up space' one after another, and there will be an offensive and defensive battle between bacteria." Wei Zhong said, the team In this study, it was found that some of the indigenous bacteria in the soil are the "helpers" of R. solanacearum, and some are the "enemies" of R. solanacearum. The interaction between these indigenous bacteria and their obligate phages can also indirectly affect plant health.
For example, some indigenous bacteria can inhibit R. solanacearum from "doing evil", while the infection and suppression of its obligate phages weakens their power, making R. solanacearum more rampant, thus aggravating the disease.
Different phages mix and match in soil like a "cocktail", affecting plant health.
"This inspires us to fully tap soil phage resources, study the mechanism of action of different phages, and the interaction between phages, and use different phages to jointly inhibit soil pathogenic bacteria." Wei Zhong explained.
Empowering new technologies, phage therapy may enhance its power
Compared with broad-spectrum antibacterial antibiotics, phage therapy has strong specificity and can accurately target a certain type of pathogenic bacteria.
However, phage therapy also faces some technical challenges.
"Similar to the use of antibiotics, phage therapy will inevitably induce resistance in target bacteria. Moreover, pathogenic bacteria are constantly mutating, and resistance will change accordingly. This requires research on pathogenic bacteria with different characteristics and continuous screening of phages , for precise treatment." Wei Zhong said.
In addition to natural barriers to phage infection, bacteria have also evolved a series of anti-phage systems to prevent phage infection.
Therefore, the application of a single phage is often unable to effectively inhibit a variety of pathogenic bacteria in the environment, and phage formulations targeting different pathogenic bacteria are required.
Even though pathogenic bacteria have thousands of faces and can change "seventy-two", "the devil is one foot tall, and the way is one foot tall."
Wei Zhong said that researchers are currently trying various ways to inhibit pathogenic bacteria from doing evil.
"The first is to establish a phage resource library. In recent years, our team has established a national soil-borne R. solanacearum obligate phage resource library. The library contains thousands of strains of R. solanacearum and five or six hundred R. solanacearum specialists that we have collected from across the country. phages.” Wei Zhong said that with the resource library, it is possible to combine culturomics, experimental evolution, machine learning, etc., to build a model for genome prediction of phage resistance, and to select different pathogenic bacteria that can infect different pathogenic bacteria or the same pathogenic bacteria. For the phages of resistant mutants, a phage "cocktail" formula is configured to combine different phages to kill pathogenic bacteria in a targeted manner.
"Secondly, with the development of synthetic biology and the deepening understanding of the infection mechanism of phages, phages can be directionally modified through gene editing, such as changing and expanding the host range of phages and enhancing the lysis efficiency of phages." Wei Zhong said.
Artificial intelligence also opens up more possibilities for improving the effectiveness of phages.
Wei Zhong believes that the variation of each pathogenic bacterium is limited, and artificial intelligence can judge the possibility of gene mutation and pathogenicity of pathogenic bacteria after accumulating a large amount of experimental data and machine learning, and screen and design corresponding phages accordingly .
"Although phage therapy still faces many technical challenges, taking advantage of its microecological optimization is one of the important ways to solve the harm of soil pathogenic bacteria and improve the health of the soil-plant system." Shen Qirong said.