Bacteriophages, often called phages, are viruses that specifically infect and replicate within bacteria. These microscopic entities are among the most abundant biological agents on Earth, found wherever bacteria exist, from soil to the human gut. Among the diverse array of phages, the T4 bacteriophage stands out as one of the most thoroughly investigated and iconic examples. Its study has been instrumental in advancing our understanding of fundamental biological processes.
Structure of T4 Bacteriophage
The T4 bacteriophage possesses a complex structure, resembling a miniature lunar lander. It consists of an elongated icosahedral head, a contractile tail, and a baseplate with attached tail fibers. The head encapsulates the phage’s genetic material, a double-stranded DNA genome that is about 169 kilobase pairs in length.
Attached to the head is a hollow, contractile tail. This tail is surrounded by a sheath that contracts during the infection process. At the tail’s distal end is a hexagonal baseplate, to which six long tail fibers are connected. These long tail fibers act as initial sensors, recognizing specific receptor molecules on the surface of the host bacterium. Additionally, six short tail fibers are present beneath the baseplate, which unfold upon host recognition to increase infection efficiency.
T4 Bacteriophage Life Cycle
The T4 bacteriophage exclusively undergoes a lytic life cycle, meaning it infects a bacterial host, replicates, and then causes the host cell to burst, releasing new phages. This process begins with adsorption, where the T4 phage attaches to the surface of a susceptible bacterial cell. The long tail fibers bind to specific receptors on the bacterial outer membrane. This binding triggers a signal to the baseplate, causing the short tail fibers to irreversibly attach to the cell surface.
Following adsorption, the phage initiates penetration. The baseplate undergoes a conformational change, and the tail sheath contracts, drilling a puncture into the bacterial outer membrane. Enzymes present in the tail degrade the bacterial cell wall, allowing the tail core to enter the host cell. The phage then injects its double-stranded DNA genome directly into the bacterial cytoplasm, leaving the empty capsid outside the cell.
Once inside the host, the biosynthesis phase begins. The phage DNA takes over the bacterial cell’s machinery, shutting down host DNA synthesis and directing the production of phage-specific proteins and replication of its own DNA. Early proteins degrade host DNA, while late proteins form the structural components of new phage particles.
As phage components accumulate, assembly occurs, where newly synthesized heads, tails, and tail fibers assemble into mature T4 virions. Finally, during lysis, the phage produces enzymes that weaken the bacterial cell wall, leading to its rupture. This releases T4 progeny phages, which are then free to infect other bacterial cells, continuing the cycle.
Significance of T4 Bacteriophage
The T4 bacteriophage has played a significant role in the history of molecular biology, contributing to foundational discoveries about genetic information. A notable example is the Hershey-Chase experiment in 1952, which utilized T2 bacteriophages (structurally similar to T4) to demonstrate that DNA, not protein, carries genetic information. By labeling phage DNA with radioactive phosphorus and phage protein with radioactive sulfur, they showed that only the DNA entered the bacterial cell to direct the synthesis of new phages, providing compelling evidence for DNA as the hereditary material.
Beyond its historical contributions, T4 bacteriophage remains relevant in contemporary research and has practical applications. It serves as a valuable tool in genetic engineering, used to modify its genome for various purposes, including delivering gene-editing tools. Its large capsid capacity makes it a potential vehicle for gene therapy, such as delivering complex genes for treating diseases.
The T4 phage is also used for phage therapy, an alternative approach to combat bacterial infections, particularly those caused by antibiotic-resistant bacteria. Phages specifically target and destroy bacterial cells while being harmless to human cells, offering a precise treatment option. Research also explores T4 as a platform for vaccine development, using its capsid to display antigens and elicit strong immune responses. These diverse applications underscore the enduring scientific and therapeutic importance of the T4 bacteriophage.