Bacteriophages: Promising Stars in the Field of Microbial Pesticides
In the family of microbial pesticides, viral preparations play an important role and are mainly divided into two categories: bacteriophages for controlling plant bacterial diseases and insect viruses for controlling pests. Among them, bacteriophages, as viruses that specifically infect bacteria, are emerging as a new hope for solving the problems in controlling plant bacterial diseases due to their unique advantage of precise targeting. Although insect virus insecticides have been applied for many years, the large-scale application of bacteriophages in plant protection is still in the ascending stage, and their development potential and practical challenges are worthy of in-depth discussion. The control mechanism of bacteriophages exhibits high specificity and efficiency. They achieve precise infection by specifically binding to receptors on the surface of target bacteria. After entering the bacteria, they hijack the host metabolic system for their own reproduction, and eventually cause the bacteria to lyse and die. The released new bacteriophages can continue to attack other harmful bacteria. This control method based on natural ecological cycles can not only efficiently eliminate pathogenic bacteria but also avoid damaging beneficial microorganisms in the soil, crops and the environment, which perfectly meets the core requirements of green agriculture for pest and disease control. Compared with chemical fungicides, the greatest advantage of bacteriophages lies in their effectiveness against drug-resistant bacteria. With the long-term abuse of chemical pesticides and antibiotics, the problem of drug resistance of plant bacterial diseases has become increasingly prominent. The targeted effect of bacteriophages enables them to effectively address this problem. At the same time, they can be applied in various flexible ways, such as foliar spraying, seed coating and soil treatment, showing strong adaptability.
In the family of microbial pesticides, viral preparations hold an important position and are mainly classified into two types: bacteriophages used to control plant bacterial diseases and insect viruses for pest control. Among these, bacteriophages, as viruses that specifically invade bacteria, are becoming a new hope for solving the challenges in controlling plant bacterial diseases due to their unique advantage of precise targeting. Although insect virus insecticides have been in use for many years, the large-scale application of bacteriophages in plant protection is still in the developing stage, and their development potential and practical challenges deserve in-depth exploration.
The exploration of using bacteriophages to control plant diseases can be traced back to 1924, when Hemstreet and Mallmann attempted to control Xanthomonas using filtrate from rotten cabbage containing bacteriophages. However, with the expansion of application scope, improvement of usability and enhancement of reliability of chemical fungicides, research on bacteriophages once fell into a slump. Entering the 21st century, breakthroughs in biotechnology have renewed interest in bacteriophage research, and the commercialization process has accelerated significantly in the past decade. In 2018, the U.S. Environmental Protection Agency (EPA) approved the registration of two bacteriophage preparations from OmniLytics for the control of fire blight in apples/pears and citrus canker. These two products were put on the market in 2019. Meanwhile, XylPhi-PD developed by Otsuka Pharmaceutical of Japan also obtained registration in California, USA in the same year for controlling Pierce's disease of grapes. In recent years, the global bacteriophage industry has shown explosive growth. In 2023, Israel's EcoPhage submitted a registration application for GoldenEco, which targets bacterial diseases in tomatoes and bell peppers. In 2024, the company reached an agreement with Maian to enter the Brazilian market. Domestic enterprises have also taken active actions. In 2024, Liming Co., Ltd. and Xiamen Changke Biology signed a strategic cooperation agreement, and Green Agriculture Biotechnology achieved the industrialization of a series of bacteriophage products such as "Xiaoqingning" and "Kuiyangning" for major plant diseases like bacterial wilt and canker. 2025 marks a milestone year: Green Agriculture Biotechnology completed a multi-million-yuan Pre-A round of financing; the Xanthomonas axonopodis pv. citri bacteriophage YHC5 developed by Phage Biotech (Nanjing) Co., Ltd. became China's first registered bacteriophage-based biopesticide for controlling citrus canker; EcoPhage also submitted a registration application for EcoFire, a product for controlling fire blight in pears and apples.
Despite the sound development momentum of the industry, the popularity of bacteriophages in plant protection applications is still relatively low compared with insect virus insecticides such as nuclear polyhedrosis viruses. This phenomenon is affected by both market perception and technical accumulation. From the perspective of market acceptance, the damage caused by insect pests is more intuitive, and the market education for related control products is mature. Although destructive plant bacterial diseases such as bacterial wilt and canker cause great harm, they could be controlled to a certain extent by chemical pesticides, especially antibiotics, in the past. The market demand for bacteriophages has gradually emerged only as the drug resistance of pesticides and antibiotics has become increasingly serious. Therefore, market education and technical accumulation for bacteriophages started relatively late. From the perspective of industrial development cycle, the first batch of insect virus insecticides came out as early as the 1970s and has been gradually accepted by the market. However, commercial bacteriophage biopesticides have only been launched in the past decade and are still in the early stage of market education and farmer awareness cultivation. Although the application method of this new technology is the same as that of other pesticides, its uniqueness requires time for farmers to learn, implement and effectively integrate into their practices. However, this situation varies by region. In countries with high-intensity intensive agriculture such as the United States and South Korea, bacteriophages have been relatively widely applied. In addition to market factors, the development of bacteriophage products also faces three core technical bottlenecks. Firstly, it is the screening of "elite bacteriophages". There are abundant bacteriophage resources in nature, but it is extremely difficult to screen out high-quality strains with broad lytic spectrum, strong lytic ability, high culture efficiency and strong stress resistance. Secondly, it is the development of resistance control technology. Bacteria can also evolve resistance to bacteriophages. The ability to solve the problem of bacteriophage resistance is crucial to the long-term effectiveness of products. The "super cocktail" technology independently developed by Ruitong Biology is one of the world's leading solutions. Large-scale production process is another major barrier. The cultivation of bacteriophages requires living host bacteria as the "culture medium", which is much more complex than the production of chemical pesticides. It is extremely challenging to achieve large-scale production with high titer, low cost and no miscellaneous bacterial contamination. The factory under Green Agriculture Biotechnology in China has passed the GMP static acceptance for bacteriophage preparations, possessing the capability of standardized production and high-standard quality control. Internationally, enterprises such as EcoPhage are also tackling the problem that bacteriophages are sensitive to environmental factors such as high temperature, ultraviolet radiation and extreme pH values, clearing the way for large-scale production. In response to the characteristic of bacteriophages being prone to inactivation, enterprises have developed diversified technical solutions. EcoPhage adopts a dual strategy of "screening optimization + formulation innovation". On one hand, it optimizes bacteriophage screening through its R&D platform and strengthens the synergy of "cocktail" formulations. On the other hand, it develops liquid and dry powder formulations, adding protective ingredients to improve environmental tolerance and shelf life. Green Agriculture Biotechnology focuses on the research and development of stabilizers. Through independently developed formulations, it ensures the stability of bacteriophages throughout the storage and application process, providing a guarantee for the field efficacy of products. The breakthroughs in these formulation technologies have effectively made up for the insufficient stability of bacteriophages themselves and laid a foundation for their field application. Cost control is also a key factor for the large-scale application of bacteriophages. Among them, the purification process is the core of production costs. The traditional experimental centrifugal sedimentation method has a purification cycle of up to 3 days, resulting in high labor and consumable costs. Green Agriculture Biotechnology has achieved the upgrading of large-scale purification systems through joint R&D with medical equipment enterprises, increasing efficiency by 20 times while significantly reducing costs. In the long run, the key to cost reduction lies in improving the titer of the original drug, which depends on three core technologies: screening high-quality strains with high burst size and high matching degree, optimizing culture parameters, and improving medium formulations. EcoPhage, on the other hand, starts with process optimization and scale effect. It reduces unit costs by improving fermentation processes and formulation schemes. With the expansion of production scale, there will be more room for cost reduction.
Facing many challenges, building a large and diverse bacteriophage library has become a core competitive advantage for the industry to break through bottlenecks. The construction process of Green Agriculture Biotechnology is highly representative: it extensively collects samples from pathogen-dense areas such as soil, diseased plants and water sources in affected fields across major agricultural regions in China; simultaneously, it establishes a host bacteria library covering tens of thousands of target pathogenic bacteria from different regions and crop sources; it realizes the isolation and enrichment of bacteriophages through laboratory co-cultivation; then screens out "elite bacteriophages" through high-throughput screening processes such as lytic spectrum determination, biological characteristic identification and genome sequencing; finally, it preserves the qualified bacteriophages in the library through ultra-low temperature freezing or freeze-drying technology. This dynamically updated bacteriophage library can quickly adjust the "cocktail" formula according to the population structure of pathogenic bacteria in different regions, improving the precision of control. EcoPhage is also building its own bacteriophage library and establishing a supporting database to optimize the development process and enhance product feasibility through data accumulation. On this basis, current bacteriophage research also focuses on four hot directions to promote continuous technological iteration: first, the optimization of precise "cocktail" therapy, which uses genomics, bioinformatics and machine learning technologies to design formulas with stronger synergy and predict the evolutionary path of resistance; second, the application of bacteriophage-encoded proteins, which extracts lytic enzymes and tail fiber proteins from bacteriophages to develop new biopesticides, breaking the host range limitation of traditional bacteriophages; third, the research and development of engineered bacteriophages, which modifies the genome through synthetic biology technology to achieve functional upgrades such as expanding the host range and enhancing the ability to penetrate biofilms; fourth, the development of synergistic control technology, which explores the combined application mode of bacteriophages with antibiotics, beneficial microorganisms and low-dose chemical pesticides to achieve the goal of synergism and reduction. Enterprises such as EcoPhage are also optimizing formulations and application methods, striving to integrate bacteriophage products into traditional spraying schemes and replace the application of copper preparations and antibiotics.
In general, bacteriophage biopesticides have broad prospects in the development of green agriculture due to their core advantages such as precise targeting, environmental friendliness and outstanding ability in drug resistance management. Although they currently face challenges such as insufficient market awareness, high technical barriers and difficult cost control, these bottlenecks are gradually being broken with the continuous improvement of screening technology, formulation process and large-scale production capacity. From the industrial signals, the active layout of domestic and foreign enterprises, the vitality of financing activities and the increasing number of registered products all indicate that the bacteriophage industry has entered a period of accelerated development. With the deepening of research and popularization of application, bacteriophages are expected to become the main products for controlling plant bacterial diseases, providing core technical support for the green transformation of agriculture and opening a new chapter in sustainable plant protection.