BACTERIOFAGO T4 PDF

The T4 genome is terminally redundant and is first replicated as a unit, then several genomic units are recombined end-to-end to form a concatemer. When packaged, the concatemer is cut at unspecific positions of the same length, leading to several genomes that represent circular permutations of the original. The DNA genome is held in an icosahedral head, also known as a capsid. Myoviridae phages like T4 have complex contractile tail structures with a large number of proteins involved in the tail assembly and function.

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They had widespread use, including treatment of soldiers in the Red Army. However, they were abandoned for general use in the West for several reasons: Antibiotics were discovered and marketed widely.

They were easier to make, store, and to prescribe. Medical trials of phages were carried out, but a basic lack of understanding raised questions about the validity of these trials. The first regulated, randomized, double-blind clinical trial was reported in the Journal of Wound Care in June , which evaluated the safety and efficacy of a bacteriophage cocktail to treat infected venous ulcers of the leg in human patients. The authors explained that the use of certain chemicals that are part of standard wound care e.

Additionally, there have been numerous animal and other experimental clinical trials evaluating the efficacy of bacteriophages for various diseases, such as infected burns and wounds, and cystic fibrosis associated lung infections, among others. Mice treated with the phage cocktail showed a 2. Without effective antibiotics the patient was subjected to phage therapy using a phage cocktail containing nine different phages that had been demonstrated to be effective against MDR A.

Dairy industry — Bacteriophages present in the environment can cause fermentation failures of cheese starter cultures. In order to avoid this, mixed-strain starter cultures and culture rotation regimes can be used.

The test returns results in about five hours, compared to two to three days for standard microbial identification and susceptibility test methods. It was the first accelerated antibiotic-susceptibility test approved by the FDA. Other uses include spray application in horticulture for protecting plants and vegetable produce from decay and the spread of bacterial disease. Other applications for bacteriophages are as biocides for environmental surfaces, e.

The technology for phages to be applied to dry surfaces, e. Clinical trials reported in Clinical Otolaryngology [19] show success in veterinary treatment of pet dogs with otitis. The SEPTIC bacterium sensing and identification method uses the ion emission and its dynamics during phage infection and offers high specificity and speed for detection. Each phage genome encodes the variant of the protein displayed on its surface hence the name , providing a link between the peptide variant and its encoding gene.

Variant phages from the library may be selected through their binding affinity to an immobilized molecule e. The bound, selected phages can be multiplied by reinfecting a susceptible bacterial strain, thus allowing them to retrieve the peptides encoded in them for further study.

With lytic phages such as the T4 phage , bacterial cells are broken open lysed and destroyed after immediate replication of the virion. As soon as the cell is destroyed, the phage progeny can find new hosts to infect.

Lytic phages are more suitable for phage therapy. Some lytic phages undergo a phenomenon known as lysis inhibition, where completed phage progeny will not immediately lyse out of the cell if extracellular phage concentrations are high.

This mechanism is not identical to that of temperate phage going dormant and usually, is temporary. In contrast, the lysogenic cycle does not result in immediate lysing of the host cell.

Those phages able to undergo lysogeny are known as temperate phages. Their viral genome will integrate with host DNA and replicate along with it, relatively harmlessly, or may even become established as a plasmid. The virus remains dormant until host conditions deteriorate, perhaps due to depletion of nutrients, then, the endogenous phages known as prophages become active.

At this point they initiate the reproductive cycle, resulting in lysis of the host cell. As the lysogenic cycle allows the host cell to continue to survive and reproduce, the virus is replicated in all offspring of the cell. An example of a bacteriophage known to follow the lysogenic cycle and the lytic cycle is the phage lambda of E. Examples are the conversion of harmless strains of Corynebacterium diphtheriae or Vibrio cholerae by bacteriophages, to highly virulent ones that cause diphtheria or cholera , respectively.

Polysaccharide-degrading enzymes, like endolysins are virion-associated proteins to enzymatically degrade the capsular outer layer of their hosts, at the initial step of a tightly programmed phage infection process. Host growth conditions also influence the ability of the phage to attach and invade them. Myovirus bacteriophages use a hypodermic syringe -like motion to inject their genetic material into the cell. After contacting the appropriate receptor, the tail fibers flex to bring the base plate closer to the surface of the cell.

This is known as reversible binding. Once attached completely, irreversible binding is initiated and the tail contracts, possibly with the help of ATP , present in the tail, [4] injecting genetic material through the bacterial membrane. The injection is accomplished through a sort of bending motion in the shaft by going to the side, contracting closer to the cell and pushing back up. Podoviruses lack an elongated tail sheath like that of a myovirus, so instead, they use their small, tooth-like tail fibers enzymatically to degrade a portion of the cell membrane before inserting their genetic material.

Synthesis of proteins and nucleic acid[ edit ] Within minutes, bacterial ribosomes start translating viral mRNA into protein. These products go on to become part of new virions within the cell, helper proteins that contribute to the assemblage of new virions, or proteins involved in cell lysis. In , Walter Fiers University of Ghent , Belgium was the first to establish the complete nucleotide sequence of a gene and in , of the viral genome of bacteriophage MS2.

The base plates are assembled first, with the tails being built upon them afterward. The head capsids, constructed separately, will spontaneously assemble with the tails. The DNA is packed efficiently within the heads. The whole process takes about 15 minutes. Release of virions[ edit ] Phages may be released via cell lysis, by extrusion, or, in a few cases, by budding. Lysis, by tailed phages, is achieved by an enzyme called endolysin , which attacks and breaks down the cell wall peptidoglycan.

An altogether different phage type, the filamentous phage , make the host cell continually secrete new virus particles. Released virions are described as free, and, unless defective, are capable of infecting a new bacterium. Budding is associated with certain Mycoplasma phages. In contrast to virion release, phages displaying a lysogenic cycle do not kill the host but, rather, become long-term residents as prophage.

Arbitrium is the name given to this protein by the researchers who discovered it. RNA phage such as MS2 have the smallest genomes, of only a few kilobases. However, some DNA phage such as T4 may have large genomes with hundreds of genes; the size and shape of the capsid varies along with the size of the genome.

These modules may be found in other phage species in different arrangements. Mycobacteriophages , bacteriophages with mycobacterial hosts, have provided excellent examples of this mosaicism.

In these mycobacteriophages, genetic assortment may be the result of repeated instances of site-specific recombination and illegitimate recombination the result of phage genome acquisition of bacterial host genetic sequences.

As a consequence, the transcription pattern of the infected bacterium may change considerably. Many of these effects are probably indirect, hence the challenge becomes to identify the direct interactions among bacteria and phage. For instance, bacteriophage lambda was found to interact with its host, E. However, a large-scale study revealed 62 interactions, most of which were new.

Again, the significance of many of these interactions remains unclear, but these studies suggest that there most likely are several key interactions and many indirect interactions whose role remains uncharacterized. The use of phages is preferred to the more conventional dye marker because they are significantly less absorbed when passing through ground waters and they are readily detected at very low concentrations.

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