Bacteriophages

Bacteriophages, or phages, are viruses that specifically infect bacteria. Since their discovery in the early 20th century, they have become essential tools in microbiological research and therapeutic innovation. Bacteriophages are highly specialized for their bacterial hosts, exhibiting diverse structures and infection strategies that influence bacterial population dynamics.

Creative Enzymes offers a wide range of highly effective bacteriophage products, both bacterial-specific and well-studied mixtures of multiple bacteriophages, to address bacterial problems in agriculture, livestock, aquaculture and food.

Overview of Bacteriophages

A bacteriophage is a virus that infects and replicates within bacteria and archaea. In fact, the word "bacteriophage" literally means "bacteria eater" because bacteriophages destroy their host cells. They are ubiquitous in the environment and are recognized as the most abundant biological agents on Earth. They are extremely diverse in size, morphology and genomic organization. However, they all consist of a nucleic acid genome encased in a shell of phage-encoded capsid proteins, which protect the genetic material and mediate its delivery to the next host cell. Electron microscopy has allowed detailed visualization of hundreds of bacteriophage types, some of which appear to have "heads", "legs" and "tails". Despite this appearance, phages are not motile and rely on Brownian motion to reach their targets. Like all viruses, bacteriophages are very species-specific to their hosts, usually infecting only a single bacterial species or even specific strains within a species.

Structure of Bacteriophages

Most bacteriophages have a characteristic head and tail structure. The head, often icosahedral, contains the viral genetic material, which can be DNA or RNA, either single or double stranded. The tail, which varies greatly in shape, plays a critical role in attaching to the bacterial cell wall and delivering the genetic material into the host. For example, some phages have short, rigid tails, while others have long, flexible tails capable of puncturing cell walls for genetic injection. Some phages have additional structural components that enhance stability or host attachment. Specific proteins on the bacteriophage surface help recognize and bind to bacterial receptors, ensuring precise host targeting and enhancing specificity.

Fig. 1: The structure of a typical myovirus bacteriophage.

Classification of Bacteriophages

Bacteriophages are classified based on their morphology, genome type, and infection strategies. The International Committee on Taxonomy of Viruses (ICTV) classifies phages into several families, the most common being Myoviridae, Siphoviridae, and Podoviridae, which are distinguished by their tail structures. Myoviridae phages have long, contractile tails, Siphoviridae phages have long, non-contractile tails, and Podoviridae phages have short tails. In addition to these bacteriophages, several other phages are shown in the diagram below, along with their nucleic acid type (double/single-stranded DNA).

Fig. 2: Basic classes of bacteriophages (Emencheta et al., 2024).

Bacteriophage Life Cycles

Bacteriophages follow two main life cycles: the lytic and lysogenic cycles.

• Lytic Cycle: A bacteriophage injects its genetic material into a bacterial host, commandeering the cell to produce new bacteriophage particles. This process ends with the rupture of the host cell, releasing the phage progeny to infect new bacteria. Lytic phages are virulent and valuable in therapies targeting bacterial infections.
• Lysogenic Cycle: In contrast, the lysogenic cycle allows the phage to integrate its genetic material into the bacterial genome, forming what is known as a prophage. The prophage can replicate along with the bacterial DNA during cell division and remain dormant until certain environmental triggers cause it to enter the lytic cycle. Phages that undergo the lysogenic cycle are known as temperate phages and have the potential to transfer genetic material to bacteria, sometimes carrying genes that enhance bacterial pathogenicity, a phenomenon known as lysogenic conversion.

Fig. 3: Diagram of the bacteriophage's life cycle Both of the lytic and lysogenic life cycles involve phage attachment to the host bacterial cell. Then the phage DNA selects to enter the bacterial cell either through the lytic cycle or the lysogenic cycle. In the lytic cycle, consequent multiplication and release of mature viruses follow the bacterial lysis. The lysogenic cycle involves integration of the bacteriophage's genome into the genome of the host bacteria; in this condition it is known as a prophage (Bisen et al., 2024).

Applications of Bacteriophages

Bacteriophages have a wide range of applications, from medical therapeutics to agriculture and biotechnology.

Phage Therapy

Phage therapy, or the use of bacterial phages to treat antibiotic-resistant bacteria, is a topic that's been revived by new strains of bacteria. Phages are highly specific to their target bacteria, minimizing harm to beneficial microbiota and reducing side effects. Phage therapy has also worked for treating infections that don't respond to conventional antibiotics (especially multidrug-resistant bacteria). Clinical trials are ongoing, particularly in wound infections, respiratory diseases and gastroenterology.

Biocontrol in Agriculture

Bacteriophages are used in agriculture to control bacterial pathogens in crops and livestock. For example, phages are applied to crops to prevent bacterial diseases without the use of chemical pesticides. Phages are also used as biocontrol in fish farming to mitigate bacterial infections that can devastate entire fish populations.

Food Safety

Bacteriophages are used in the food industry to reduce bacterial contamination. They are used to target pathogens such as Listeria, Salmonella, and E. coli in food products, providing an alternative to chemical preservatives and improving food safety.

Molecular Biology and Biotechnology

Bacteriophages are important tools in molecular biology and genetic engineering. Phages such as M13, λ phage, and T7 have been used to develop cloning vectors and provide systems for gene manipulation, protein expression, and sequencing. Phage display, a technique in which peptides or proteins are displayed on the surface of phages, is widely used in research and drug discovery to identify binding partners and develop new therapeutics.

Fig. 4: Bacteriophages—Natural Killers. Functions of bacteriophages in human health, animal health and environmental health (Lavilla et al., 2023).

Product Line Overview

At Creative Enzymes, our bacteriophage-based products address specific bacterial challenges, promoting sustainability and efficiency in agriculture, aquaculture, and food safety.

Livestock and Aquaculture Solutions

• Aquaculture Gut Protector: Enhances gut health and boosts the immune response of aquatic species, leading to improved growth and disease resistance.
• Composite Aquaculture Antibacterial Agent: Targets resistant pathogens in aquaculture, specifically Gram-negative bacteria such as Aeromonas, Edwardsiella, Citrobacter and Escherichia coli.
• Vibrio harveyi Lysate: Specifically formulated for combating Vibrio harveyi and related pathogens (V. alginolyticus), it reduces bacterial loads and mortality in fish and shellfish, promoting aquaculture sustainability.
• Phage Mate: A tailored solution for controlling Gram-positive and Gram-negative bacteria, including Vibrio, Aeromonas, Edwardsiella, Streptococcus and Nocardia, for healthier aquaculture systems.
• Compound Bacterial Lysate: A broad-spectrum antibacterial solution combining lysates from multiple bacterial species, ideal for high-density farming systems to prevent disease outbreaks.
• Aquaculture Intestinal and Liver Protective Agent: A specially formulated solution to support intestinal and liver health in aquatic species, reducing infection rates and improving nutrient utilization, leading to healthier, more productive aquaculture.
• Vibrio alginolyticus Lysate: Targets Vibrio alginolyticus, protecting aquatic species from this common pathogen and reducing the prevalence of bacterial infections in aquaculture.
• Vibrio parahaemolyticus lysate: Designed for the aquaculture industry, this lysate specifically targets Vibrio parahaemolyticus, improving health outcomes in aquaculture systems susceptible to bacterial outbreaks.
• Bacteriocin TS: A natural bioactive antimicrobial and can be used in livestock industry to improve the intestinal health level of animals to regulate the microflora balance, enhancing animal immunity and resistance to stress.

Agriculture Solutions

• Bacteriophage Modifier for Agricultural Cultivation Environment: Reduces harmful soil bacteria, promoting healthier crops while minimizing the need for chemical inputs.
• Elisabethella Lysate: Specially prepared to target harmful Elisabethella bacteria, this lysate provides a targeted approach for industries where this bacterial genus may pose a health risk, including agriculture and animal husbandry.

Food Safety Solutions

• Salmonella Bacteriophages: A food-grade bacteriophage solution designed to target Salmonella, ensuring food safety in animal products by reducing bacterial contamination risks without compromising quality.

Our precision-engineered bacteriophage solutions reduce dependence on antibiotics and chemicals while promoting healthier ecosystems. By addressing bacterial challenges in a natural way, we provide effective, sustainable tools for modern production systems in agriculture, aquaculture and food safety. Contact us today to find the perfect bacteriophages solution for your needs!