Lesson 14: Bacteriophages and their applications

Bacteriophages, or phages, are viruses that infect bacteria and come in a wide variety of types, each with unique characteristics, life cycles, and applications. Here’s a detailed overview that includes their classification, structure, life cycles, growth, regulation, and applications.

1. Classification: Families and Genera

Bacteriophages are classified based on their morphology, genetic material, and replication strategies. They are grouped into several families, with each family containing different genera and species that infect specific bacterial hosts.

Myoviridae

• Morphology: These phages have a contractile tail, an icosahedral head, and double-stranded DNA (dsDNA). The tail contracts during infection to inject the DNA into the bacterial host.
• Life Cycle: Most are lytic, rapidly killing their bacterial hosts.
• Genera:
  • T4likevirus: Includes T4 phage, which infects Escherichia coli and has been widely studied for its genetics and structure.
  • P1virus: Includes phage P1, which infects E. coli and some other enterobacteria.
• Host Range: Broad, often targeting E. coli and related bacteria.

Siphoviridae

• Morphology: These phages have a long, non-contractile, flexible tail and an icosahedral head, with dsDNA. The tail serves as a tube for DNA injection without contracting.
• Life Cycle: Can be lytic or lysogenic, integrating into the host genome in the lysogenic cycle.
• Genera:
  • Lambdalikevirus: Includes the Lambda phage, which infects E. coli and is a model for studying lysogeny.
  • L5virus: Includes L5, which infects Mycobacterium tuberculosis and is used in tuberculosis research.
• Host Range: Often specific to certain bacterial families, like enterobacteria.

Podoviridae

• Morphology: These phages have a short, non-contractile tail and an icosahedral head, with dsDNA.
• Life Cycle: Primarily lytic.
• Genera:
  • T7virus: Includes T7 phage, infecting E. coli, and has been important in molecular biology research.
  • P22virus: Includes P22 phage, which infects Salmonella species and is a model system for studying genetic recombination.
• Host Range: Typically narrow, targeting specific bacterial species.

Inoviridae

• Morphology: These phages are filamentous, with a flexible rod-like structure, and contain single-stranded DNA (ssDNA).
• Life Cycle: Usually chronic infection without killing the host; phages are released slowly from the host cell, which remains intact.
• Genera:
  • Inovirus: Includes M13, which infects E. coli and is widely used in phage display technology and genetic engineering.
  • Ff phages: Includes F1 and Fd phages, also infecting E. coli and related bacteria.
• Host Range: Primarily targets bacteria with specific pili (e.g., F-pili in E. coli).

Leviviridae

• Morphology: Small, spherical, with single-stranded RNA (ssRNA).
• Life Cycle: Lytic, infecting host cells and releasing progeny without a lysogenic phase.
• Genera:
  • Levivirus: Includes phage MS2, which infects E. coli and has been extensively studied for its RNA replication.
  • Allolevivirus: Includes Qβ phage, another model RNA phage for molecular biology.
• Host Range: Narrow, typically limited to E. coli and related bacteria.

Microviridae

• Morphology: Small, icosahedral, containing circular ssDNA.
• Life Cycle: Lytic, rapidly killing the host cell.
• Genera:
  • Microvirus: Includes φX174, a phage infecting E. coli and other enterobacteria; it was the first genome to be sequenced and is a model in virology.
• Host Range: Primarily targets E. coli and some other bacteria in the family Enterobacteriaceae.

Corticoviridae

• Morphology: Icosahedral, non-enveloped, containing circular dsDNA.
• Life Cycle: Primarily lytic.
• Genera:
  • Corticovirus: Includes phage PM2, which infects marine bacteria like Pseudomonas and has been studied for its unique structure and lipid envelope.
• Host Range: Targets specific marine bacteria, with a relatively narrow range.

Tectiviridae

• Morphology: Icosahedral, with an internal membrane surrounding dsDNA.
• Life Cycle: Lytic or lysogenic, depending on environmental conditions.
• Genera:
  • Tectivirus: Includes PRD1, a phage that infects Gram-negative bacteria, including Escherichia coli and Salmonella.
• Host Range: Generally targets Gram-negative bacteria.

Cystoviridae

• Morphology: Enveloped, spherical, containing segmented dsRNA genomes.
• Life Cycle: Lytic, infecting host cells with progeny release.
• Genera:
  • Cystovirus: Includes φ6 phage, which infects Pseudomonas syringae and has served as a model for studying segmented RNA viruses.
• Host Range: Primarily infects Pseudomonas species.

Innovative Families (e.g., Ackermannviridae, Herelleviridae)

• These families include recently discovered or reclassified bacteriophages and represent new genera and diversity within phages. For example, Ackermannviridae and Herelleviridae contain large and complex phages that infect Gram-positive bacteria such as Bacillus and Clostridium species.

2. Structure and composition of Bacteriophages

Head (Capsid)

• Structure: The head, also called the capsid, is an icosahedral (20-sided) or prolate structure that houses the genetic material of the phage. In many phages, the head has an icosahedral symmetry, although some, like filamentous or rod-shaped phages, have different shapes.
• Composition: Composed of capsid proteins that protect the viral genome from environmental damage. These capsid proteins self-assemble to form a stable and protective shell around the nucleic acid.
• Genetic Material: The genetic material is stored within the head and can be:
  • Double-stranded DNA (dsDNA): Most common among bacteriophages (e.g., T4 and Lambda phages).
  • Single-stranded DNA (ssDNA): Found in phages like φX174.
  • Double-stranded RNA (dsRNA): Seen in segmented genomes like φ6.
  • Single-stranded RNA (ssRNA): Found in phages like MS2.
• Function: The head acts as a storage and protection unit for the genome, ensuring its integrity until the phage can inject it into a bacterial cell.

Tail

• Structure: Not all phages have tails, but those that do can have long contractile tails (Myoviridae), long non-contractile tails (Siphoviridae), or short non-contractile tails (Podoviridae).
• Composition: The tail is typically composed of multiple protein subunits arranged in a tube-like structure that varies in length, rigidity, and function:
  • Contractile Tail: Found in Myoviridae phages, it functions like a syringe, injecting genetic material through a contraction mechanism.
  • Non-contractile Tail: Found in Siphoviridae, it forms a long, flexible structure that connects the capsid to the baseplate, assisting in attachment and DNA transfer without contraction.
• Function: The tail plays a key role in host recognition and attachment and facilitates genome injection by anchoring the phage to the host cell surface.

Baseplate

• Structure: Located at the end of the tail, the baseplate is a complex multi-protein structure with receptor-binding proteins and enzymatic components.
• Composition: Made of several proteins that can interact with bacterial surface receptors.
• Function: Acts as the “landing gear” for phages. It anchors the phage to the bacterial cell and often changes conformation upon binding, which helps initiate DNA injection. In Myoviridae phages, the baseplate contains contractile components that trigger tail contraction.

Tail Fibers or Spikes

• Structure: These are long, thin protein filaments attached to the baseplate or tail that extend outward.
• Composition: Composed of tail fiber proteins, which vary between phages depending on their host specificity.
• Function: Tail fibers help the phage recognize and attach to specific receptors on the bacterial cell surface, giving the phage its host specificity. Some phages (like T4) have multiple tail fibers that increase the strength of attachment.

Sheath (in Contractile Tailed Phages)

• Structure: The sheath is a tube-like, contractile component of the tail found in some phages, particularly Myoviridae.
• Composition: Composed of protein subunits that can contract in a coordinated manner.
• Function: The sheath contracts during the infection process, driving the internal tail tube into the host’s membrane, creating a passage for the genome to be injected into the host cell.

Internal Core (in Some Phages)

• Structure: An internal tube-like structure within the tail that acts as a pathway for DNA or RNA.
• Composition: Typically composed of core proteins that form a tube structure, which is protected by the sheath (in contractile-tailed phages).
• Function: The core acts as a conduit for transferring genetic material from the capsid into the bacterial host during infection.

Collar and Neck (in Some Phages)

• Structure: In some tailed phages, the collar and neck connect the head and tail.
• Composition: Protein complexes that stabilize the attachment between the head and tail.
• Function: Provides structural stability to the phage particle and may play a role in genome packaging.

Proteins and Enzymes

• Structural Proteins: Form the capsid, tail, tail fibers, and other components, providing stability and functionality.
• Enzymatic Proteins:
  • Lysozyme: Present in some phages like T4, which helps degrade the bacterial cell wall for genome injection.
  • Endolysin: Degrades the bacterial cell wall during the release of progeny phages, aiding in cell lysis.
  • Holins: Form holes in the bacterial membrane to assist in the release of new phages after replication.
• Replication Proteins: In phages with RNA genomes, RNA-dependent RNA polymerase is included to initiate replication immediately upon entry into the host cell.

Summary of Structure and Composition

3. Life Cycles of Bacteriophages

Phages generally follow two types of replication cycles:

• Lytic Cycle: In this cycle, the phage attaches to a bacterial cell, injects its DNA, and hijacks the bacterial machinery to replicate its genome and produce new phage particles. The host cell eventually lyses (bursts), releasing new phages that can infect other bacteria.
• 1. Attachment: Phage binds to the bacterial surface via specific receptors.
  2. Penetration: Phage injects its genetic material into the bacterial cell.
  3. Replication: Host machinery is used to replicate phage DNA and synthesize proteins.
  4. Assembly: New phage particles are assembled within the host cell.
  5. Lysis: Host cell bursts, releasing new phages to infect other bacteria.
• Lysogenic Cycle: In this cycle, the phage DNA integrates into the bacterial genome and remains dormant as a prophage. It can replicate along with the bacterial chromosome when the bacterium divides. Under certain conditions (e.g., stress), the prophage may exit the bacterial genome and enter the lytic cycle.

1. 1. Attachment and Injection: Similar to the lytic cycle.
   2. Integration: Phage DNA integrates into the host genome as a prophage, replicating passively with the host.
   3. Dormancy: The prophage remains inactive until triggered by environmental factors to excise from the host genome.
   4. Induction: Under stress, the prophage can enter the lytic cycle, leading to the production of new phage particles.

4. Growth and Propagation of Phages

The growth and propagation of bacteriophages involve specific phases that occur during their infection cycle within a bacterial host. This process typically includes the adsorption, penetration, replication, assembly, and release phases. The growth of phages can be measured quantitatively in laboratory settings using plaque assays, which allow scientists to study phage kinetics and proliferation.

Phage Infection Cycle: Stages of Growth and Propagation

a. Adsorption (Attachment)

• Process: Phages attach to specific receptors on the surface of a bacterial cell. Tail fibers or other specialized structures recognize these receptors, making this step highly specific to certain bacterial species or strains.
• Specificity: The recognition between phage and bacterial receptors dictates host range, meaning phages usually infect only specific bacterial types.

b. Penetration (Injection)

• Process: After attachment, the phage tail contracts (in contractile-tailed phages) and injects its genetic material (DNA or RNA) into the bacterial cell. Some phages rely on enzymatic action to degrade part of the bacterial cell wall, aiding in DNA entry.
• Result: The phage genome enters the bacterial cytoplasm, leaving the empty capsid outside the cell. This initiates the hijacking of the bacterial machinery.

c. Replication and Transcription

• Process: Inside the host, the phage genome directs the bacterial machinery to begin synthesizing viral components:
  • Early genes: These are transcribed and translated first and are typically involved in shutting down bacterial defenses and preparing the host cell for phage replication.
  • Replication: Phage DNA or RNA is replicated, producing multiple copies of the genome.
  • Late genes: Expressed later in the cycle, these encode structural proteins necessary for assembling new phage particles.
• Host Machinery: The bacterial ribosomes, nucleotides, and energy are all redirected toward phage production.

d. Assembly (Maturation)

• Process: New phage particles are assembled from synthesized components in the host cell. The genetic material is packaged into newly formed capsids, tails are attached, and fully assembled phages are created.
• Self-Assembly: This process is typically highly efficient and mostly driven by the intrinsic properties of phage proteins to self-assemble, requiring minimal enzymatic action.

e. Lysis and Release

• Process: Once a sufficient number of phages are assembled, specialized lytic enzymes (such as endolysins) break down the bacterial cell wall. Phage holins form pores in the bacterial membrane, leading to cell rupture.
• Result: The bacterial cell lyses, releasing the newly formed phages into the surrounding environment, where they can infect nearby bacteria.

In some cases, bacteriophages may enter a lysogenic cycle, particularly temperate phages like Lambda. In the lysogenic cycle, the phage genome integrates into the host bacterial DNA, remaining dormant until triggered to re-enter the lytic cycle under certain environmental conditions.

One-Step Growth Curve of Phages

A one-step growth curve is a method used to study the kinetics of phage infection and replication within a bacterial population. This curve consists of several key phases that describe the burst of phage propagation within a host population:

• Latent Period: The initial period after infection, during which no new phages are released. This includes the adsorption, penetration, and early stages of replication. Inside the bacterial cell, phage DNA is being replicated, and proteins are synthesized.
• Eclipse Period: Part of the latent period where phages are actively replicating and synthesizing proteins, but new, complete phage particles have not yet been assembled.
• Burst Period: Following the latent period, new phage particles are assembled, and the host cell undergoes lysis, releasing many phages at once.
• Burst Size: The number of new phages released per infected cell, typically ranging from tens to hundreds, depending on the phage and host conditions.

Laboratory Methods for Phage Growth and Propagation

a. Plaque Assay (Double-Layer Agar Assay)

• Process: A bacterial host culture and phage sample are mixed with soft agar and poured onto a solid agar plate. Phages infect bacteria, creating clear zones called plaques where cells have been lysed.
• Quantification: Plaques are counted to estimate the number of plaque-forming units (PFU), a measure of phage concentration in the sample.
• Use: Plaque assays are the standard method for determining phage titer (concentration) and are widely used in research and diagnostics.

b. Liquid Culture Propagation

• Process: Phages are added to a liquid culture of bacterial cells. Over time, phages replicate, lyse the bacterial cells, and release new phages into the medium.
• Turbidity Measurement: As the phages lyse bacteria, the culture becomes less turbid (cloudy), and this can be measured spectrophotometrically.
• Collection: Phages are collected from the lysate (liquid culture post-lysis), purified, and stored.

c. High-Density Phage Production (Fermentation)

• Process: For industrial applications, phages can be propagated in bioreactors with controlled conditions to produce high titers of phage particles.
• Applications: Common in phage therapy, biocontrol, and phage-based bioproducts, where large quantities of phages are required.

Factors Affecting Phage Growth and Propagation

• Host Bacterial Strain: Phages can only infect specific bacterial strains with compatible receptors.
• Multiplicity of Infection (MOI): The ratio of phages to bacterial cells influences growth. A high MOI can lead to rapid bacterial lysis, while a low MOI results in slower propagation.
• Temperature and pH: Optimal conditions vary by phage, with many performing best at 37°C and near-neutral pH, although some environmental phages have adapted to extreme conditions.
• Nutrient Availability: Bacterial host growth rate affects phage replication; rapidly growing cells allow for faster phage replication.

5. Regulation of life cycles of Phages

The regulation of phage life cycles—determining whether a phage enters a lytic or lysogenic cycle—is influenced by complex interactions between the phage, the bacterial host, and environmental factors. Here’s an in-depth look at the mechanisms controlling these life cycles and how they are regulated.

A. Life Cycle Determination in Temperate Phages

• Temperate Phages: These phages, such as Lambda (λ) phage, can choose between the lytic and lysogenic cycles based on environmental and host conditions. This choice is tightly regulated by genetic and molecular switches.Factors Influencing Life Cycle
  • Host Cell Health and Density: When bacterial cells are in a healthy, nutrient-rich environment, temperate phages are more likely to enter the lytic cycle, as there are abundant resources for rapid replication. Conversely, if the host cell population is low or stressed, phages may choose the lysogenic cycle to “wait out” unfavorable conditions.
  • Phage Proteins as Molecular Switches: In λ phage, the decision between the lytic and lysogenic cycle is controlled by a balance between two key regulatory proteins:
    • CI Repressor: This protein promotes lysogeny by repressing the genes required for the lytic cycle. It binds to operators in the phage genome, inhibiting lytic gene expression.
    • Cro Protein: Cro promotes the lytic cycle by inhibiting CI production, thereby allowing lytic genes to be expressed.
• Molecular Switches in λ Phage:
  • The balance between CI and Cro proteins functions as a genetic switch. When CI levels are high, lysogeny is favored, as CI blocks the expression of genes necessary for the lytic cycle. If Cro levels increase (often due to stress or DNA damage in the host cell), lytic genes are expressed, leading to cell lysis and the release of new phages.

B. Induction of the Lytic Cycle

• Environmental Stress: Phages can transition from lysogeny to lysis (called “induction”) when the host cell experiences environmental stress, such as UV light, DNA-damaging agents, or nutritional stress. These conditions signal a threat to the survival of the host and, therefore, the survival of the prophage.
• SOS Response in Bacteria: The bacterial SOS response, triggered by DNA damage, is one of the primary mechanisms that prompts the transition from the lysogenic to the lytic cycle.
  • Role of RecA Protein: In response to DNA damage, the bacterial protein RecA is activated, which then cleaves the CI repressor in λ phage, lifting repression of lytic genes and initiating the lytic cycle.
  • Result: With CI repression removed, lytic genes are expressed, phage particles are produced, and the host cell undergoes lysis, releasing new phages.

C. Regulation by Host-Phage Interactions

• Host Receptor Availability: For phages that rely on specific receptors on the bacterial cell surface, changes in receptor availability can influence phage life cycles. Some bacteria may downregulate receptor expression to prevent phage attachment and infection, indirectly influencing whether a phage can successfully enter a lytic cycle.
• Superinfection Exclusion: Some lysogenic phages express proteins that block other phages from infecting the same host. This can prevent additional phage infections, favoring the continued stability of the lysogenic state in the host cell.
• Bacterial Defense Mechanisms:
  • CRISPR-Cas System: The bacterial immune system can target and degrade foreign phage DNA, preventing infection. If phages detect or anticipate CRISPR-Cas defenses, they may modulate their life cycle accordingly.
  • Restriction-Modification Systems: Some bacteria use restriction enzymes to cut phage DNA, which can reduce successful lytic infections. Phages have evolved anti-restriction strategies to counteract this, such as modifying their DNA to evade restriction enzymes.

D. Regulation by Quorum Sensing

• Quorum Sensing in Phage: Some phages, such as the Vibrio phages, can sense host cell density and use this information to decide whether to enter the lytic or lysogenic cycle. At high host densities, lytic infection is more favorable because there are more potential hosts to infect. In low-density environments, the lysogenic cycle is preferred to ensure the phage genome persists until conditions improve.
• Example in Vibrio Phages: Certain phages infecting Vibrio cholerae have proteins that respond to quorum-sensing molecules produced by the bacterial host. When host density is high, the phage switches to the lytic cycle to produce and release progeny into the environment, maximizing the chance of infecting new hosts.

E. Nutrient Availability and Metabolic Status

• Influence of Nutrients on Phage Choice: In nutrient-rich conditions, bacteria actively grow and divide, providing a favorable environment for the lytic cycle. Under nutrient-poor conditions, the phage may enter or remain in lysogeny, “waiting” for better conditions before entering the lytic phase.
• Example in E. coli and Lambda Phage: λ phage tends to remain lysogenic in nutrient-limited environments, where bacterial replication is slow, but switches to lysis in nutrient-rich conditions, where host cells can support high levels of phage replication.

F. Genetic Determinants and Mutations in Phages

• Mutations in Regulatory Genes: Mutations in genes controlling CI and Cro proteins or their equivalents in other phages can shift the phage’s propensity for lytic or lysogenic cycles.
• Adaptive Mechanisms: Some phages adapt to changing environments by acquiring or losing genes that regulate their life cycles, making them more suited to specific environmental conditions or bacterial hosts.

6. Applications of Bacteriophages

Bacteriophages have a broad range of applications across healthcare, agriculture, biotechnology, and environmental management due to their specificity in targeting bacteria. Here’s an overview of the primary applications:

A. Phage Therapy for Treating Bacterial Infections

• Alternative to Antibiotics: Phage therapy is a promising treatment for bacterial infections, particularly antibiotic-resistant infections. Phages specifically target and kill bacteria without affecting human cells or beneficial microbiota, which minimizes side effects.
• Precision Medicine: Phages can be tailored to target specific bacterial strains, making them ideal for precision therapies, especially for multidrug-resistant bacteria such as MRSA (methicillin-resistant Staphylococcus aureus), E. coli, and Pseudomonas aeruginosa.
• Clinical Trials and Research: Phage therapy has shown success in treating chronic infections like diabetic foot ulcers, burn wounds, and cystic fibrosis lung infections. Clinical trials and expanded compassionate use programs are exploring these therapies in various countries.

B. Food Safety and Preservation

• Preventing Foodborne Illnesses: Phages are used to target pathogenic bacteria in food products, such as Listeria monocytogenes, Salmonella, and E. coli, improving food safety and reducing foodborne outbreaks.
• Application in Food Processing: Phage-based sprays and rinses are applied to meat, dairy, and produce to reduce bacterial contamination. These phages are safe to consume and can be used as natural biocontrol agents, reducing the need for chemical preservatives.
• Extending Shelf Life: By selectively targeting spoilage bacteria, phages can help extend the shelf life of perishable foods, improving food quality and reducing waste.

C. Agricultural Applications

• Biocontrol of Plant Pathogens: Phages are used to control bacterial plant diseases, such as those caused by Xanthomonas and Erwinia species, which affect crops like tomatoes, peppers, and potatoes. They provide an eco-friendly alternative to chemical pesticides.
• Protection of Aquaculture: In fish farms, phages can prevent bacterial infections caused by pathogens like Aeromonas and Vibrio, which lead to diseases in fish and shellfish. This reduces the need for antibiotics, decreasing the risk of antibiotic-resistant bacteria in aquaculture.
• Soil and Crop Health: Phage treatments can be applied to soil to reduce the bacterial load of harmful pathogens, promoting healthier crops and yields.

D. Environmental Applications

• Wastewater Treatment: Phages help control pathogenic bacteria in wastewater, reducing the bacterial load before water is discharged into the environment. They can target harmful bacteria like Escherichia coli and Pseudomonas, improving water quality.
• Bioremediation: Certain phages target bacteria involved in environmental pollution, such as oil-degrading bacteria. They can enhance bioremediation processes by ensuring that bacterial communities are balanced and functional for efficient pollutant degradation.
• Biofilm Control: Phages are effective against biofilms—structured communities of bacteria that are resistant to disinfectants. In industrial pipelines and water treatment facilities, phages help control biofilms that clog systems and harbor harmful pathogens.

E. Molecular Biology and Biotechnology Tools

• Phage Display Technology: Phage display is a technique that uses bacteriophages to study protein-protein, protein-peptide, and protein-DNA interactions. It involves expressing foreign proteins or peptides on the phage surface, allowing scientists to screen and identify binding partners for drug discovery, antibody engineering, and vaccine development.
• Genetic Engineering: Phages are widely used as vectors for genetic modification. They can deliver specific DNA sequences to bacterial cells, facilitating genetic studies and the development of bacterial strains for industrial processes.
• CRISPR-Cas System Discovery and Engineering: The CRISPR-Cas system, originally discovered as a bacterial defense against phages, has revolutionized genetic engineering. Phages are used to study and manipulate CRISPR-Cas systems, advancing gene editing technology for use in humans, animals, and plants.

F. Diagnostics and Biosensing

• Rapid Detection of Bacteria: Phage-based biosensors detect specific bacteria by taking advantage of the specificity of phage-host interactions. When a target bacterium is present, phage binding or replication can trigger a detectable signal, enabling rapid diagnostics.
• Phage Amplification Assays: Phage amplification assays detect bacterial pathogens in clinical, environmental, and food samples. In these assays, phages infect target bacteria, and their subsequent replication indicates the presence of the target bacterium.
• Lab-on-a-Chip Devices: Phage-based microfluidic devices (lab-on-a-chip) allow rapid, point-of-care bacterial detection in healthcare and food safety settings. These devices are being developed for use in hospitals, clinics, and field settings where quick results are critical.

G. Veterinary Medicine

• Treatment of Animal Infections: Phages are used to treat bacterial infections in livestock, pets, and other animals. They offer an alternative to antibiotics for treating infections in animals, reducing the risk of antibiotic-resistant bacteria transferring to humans.
• Prevention in Animal Farming: Phage treatments can prevent bacterial diseases in poultry, swine, and cattle, contributing to healthier livestock and reducing the need for preventive antibiotic use.
• Fish Health in Aquaculture: As in agriculture, phages control bacterial pathogens in fish farming, improving fish health and reducing antibiotic use in aquaculture settings.

H. Public Health and Epidemiology

• Phage Therapy for Infectious Disease Outbreaks: Phages can help contain outbreaks of bacterial diseases, especially when they are multidrug-resistant. Phage therapy has been explored for use in combating outbreaks of Shigella, Salmonella, and Vibrio cholerae.
• Control of Pathogenic Bacteria in the Environment: Phages can be applied in public settings, such as hospitals, to target and reduce the spread of harmful bacteria, lowering infection rates and supporting sanitation efforts.
• Phage Surveillance in Epidemiology: Phage-based detection methods monitor bacterial strains in healthcare and environmental settings, allowing for early detection of pathogenic bacteria and preventing widespread outbreaks.