Phage Therapy to Treat Bacterial Infections

Phage Therapy to Treat bacterial InfectionsIntroductionBaterio bacterio bacterio bacterio bacteriophagesThe word bacteriophage, which is a name for bacterial viruses, means eater of bacteria. These viruses parasitize and fling off bacteria. Pi geniusering work on the genetics of bacteriophages in the middle of the twentieth century formed the foundation of much recent research on tumor-causing viruses and other(a) kinds of wolf and base viruses. In this way bacterial viruses cave in provided an important model transcription.A bacteriophage is a bacterial parasite. By itself, a phage back end persist, hardly it cannot replicate except within a bacterial cell. more or less phages possess genes encoding a variety of proteins. (Ringo John)Discovery and SignificanceBacteriophages, viruses that infect or kill bacteria, were discovered by Frederick W. Twort in England in 1917 independently. Twort observed that bacterial colonies sometimes underwent lysis (dissolved and disappe ato mic number 18d) and that this lytic effect could be transmitted from colony to colony. Even high dilutions of physical from a lysed colony that had been passed through a bacterial filter could transmit the lytic effect. However, heating the filtrate destroyed its lytic property. From these observations Twort suggested that the lytic agent might be a virus. DHerelle rediscovered the phenomenon in 1917 (hence the term Twort dHerelle phenomenon) and coined the word bacteriophge, which means bacteria eater. He considered the filterable agent to be an invisible microbe- for suit, a virus- that was parasitic for bacteria. (Pelczar)Since the bacterial armaments of phages are well cultivated under controlled conditions, demanding relatively little in terms of time, labor, and space compared with the maintenance of plant and animal hosts, bacteriophages have received considerable attention in viral research. Furthermore, since bacteriophages are the smallest and simplest biological entit ies known which are capable of self replication, they have been widely utilise in genetic research. Much has been learned active host parasite relationship from these studies, which have provided a better understanding of plant and animal infections with viral pathogens. Thus the bacterium-bacteriophage interaction has become the model system for the theater of operations of viral pathogenicity. (Pelczar)General characteristicsBacterial viruses are widely distributed in nature. Phages exists for most, if not all, bacteria. With the proper techniques these phages can be isoalated quit easily in the laboratory.Bacteriophages, manage all viruses, are composed of a nucleic acid core surrounded by a protein coat. Bacterial viruses occurring different shapes, although many a(prenominal) have a female genital organ through which they inoculate the host cell with viral nucleic acid.There are two main figures of bacterial viruses lytic, or virulent, and temperate or avirulent. When ly tic phages infect cells, the cells resolve by producing large functions of new viruses. That is, at the end of the incubation period the host cell bursts or lyses, releasing new phages to infect other host cells. This is called a lytic cycle. In the temperate type of infection, the result is not so readily apparent. The viral nucleic acid is carried and replicated in the host bacterial cells from one generation to another without any cell lysis. However, temperate phages may spontaneously become virulent at some subsequent generation and lyse the host cells. In addition, there are some filamentous phages which simply leak out of cells without killing them.Types of BacteriophagesThere are two types of bacteriophages.Virulent phages andTemperate phagesVirulent phages - As a result of reproduction, virulent phages destroy their host.For example - T pahges or T1-T7 group of phages infect E.coli bacteria.Temperate Phages - temperate phages do not kill their host and take over its machi nery.For example - Lambda phage (Study.com)Fig -1 Fates of PhagesMorphology and StructureThe electron microscope has made it possible to determine the structural characteristics of bacterial viruses. All phages have a nucleic acid core covered by a protein coat, or capsid. The capsid is made up of microbiological subunits called capsomeres. The capsomere consists of a number of protein subunits or molecules called protomers. Figure 1 shows the fine structure and anatomy of a common morphological form of the bacteriophage, one with a head and a rat.Fig. 2 Diagrammatic representation of coliphageBacterial viruses may be grouped into six morphological typesThis type has a hexagonal head, a rigid tail with a contractile sheath, and tail fibers.This type has a hexagonal head similar to A. However, it lacks a contractile sheath, its tail is flexible, and it may or may not have tail fibers.This type is characterized by a hexagonal head and a tail shorter than the head. The tail has no con tractile sheath and may or may not have tail fibers.This type has a head made up of large capsomeres, but has no tail.This type has a head made up of small capsomeres, but has no tail.This type is filamentous.Types A, B, and C Show a morphology unique to bacteriophages. The morphological types in groups D and E are found in plant and animal viruses as well. The filamentous form of group F is found in some plant viruses.Fig 3 Types of BacteriophagesPhage StructureMost phages occur in one of two structural forms, having either cubic or helical symmetry. In overall appearance, cubic phages are regular solids or, more particular(prenominal)ally, polyhedral helical phages are rod-shaped.Polyhedral phages are icosahedral in shape. (The icosahedrons is a regular polyhedron with 20 triangular facets and 12 vertices.) This means that the capsid has 20 facets, each of which is an equilateral triangle these facets come together to form the 12 corners. In the simplest capsid, there is a capso mere at each of the 12 vertices this capsomere, which is surrounded by five other capsomeres, is termed as a penton. For example, the X174 exhibits the simple capsid. In larger and more complex capsids, the triangular facets are subdivided into a progressively larger number of equilateral triangles. Thus a capsid maybe composed of capsomeres but it is still based on the simple icosahedrons model.The elongated heads of some give chase phages are derivatives of the icosahedrons. For example the head of the T2 and T4 phages is an icosahedron elongated by one or two extra bands of hexons.Rod-shaped viruses have their capsomeres arranged helically and not in stacked rings. An example is the Bacteriophages M13.Some bacteriophages, such as the T-even coliphages (T2, T4 and T6), have very complex structures, including a head and a tail. They are said to have binal symmetry because each virion has some(prenominal) an icosahedral head and a hollow helical tail.Phage Nucleic AcidsDifferent m orphological types of phages are as well as characterized by having different nucleic acid types. All tailed phages contain double-stranded DNA. The phages with large capsomeres and the filamentous ones have single-stranded DNA. Group E phages have single-stranded RNA. The DNAs of phages are circular under certain conditions. The DNA of phage X174 is circular both in the virion and in the host cell. The DNA of phage lambda is linear in the virion, but on entering the host cell the sticky ends join to form a circle.Infection of bacteria by phagesMost bacteria are susceptible to attack by bacteriophages. A phage consists of a nucleic acid chromosome (DNA or RNA) surrounded by a coat of protein molecules. Phage types are identified not by species names but by symbols for example, phageT4, phage lambda, and so forth. During infection, phage attaches to a bacterium and injects its genetic material into the bacterial cytoplasm. The phage genetic information then takes over the machiner y of the bacterial cell by turning off the synthesis of bacterial components and redirecting the bacterial synthetic machinery to make phage components. Newly made phage heads are individually stuffed with replicates of the phage chromosome. Ultimately, many phage descendants are made and are released when the bacterial cell wall breaks open. This breaking open process is called lysis. The population of phage progeny is called the phage lysate.Commercial production of PhagesIn DHerelles laboratory against various bacterial infections five phage preparations were produced. That phage preparations are Bacte-coli-phage, Bacte-rhino-phage, Bacte-intesti phage, Bacte-pyo-phage and Bacte-staphy phage.In the United States healing(p) phages were also produced. Seven phage product for human use produced by the Eli Lilly company in the 1940s including preparations against Staphylococci, Sreptococci, E.coli, and other bacterial pathogen. These preparations contains phage-lysed, bacteriologica lly sterile broth cultures of the targeted bacteria. These preparations were used against various infections including wounds, vaginitis, acute and chronic infections of the upper respiratory tract, abscesses and mastoid infections. In most of the Western World commercial production of therapeutic phages ceased because of controversy.But in Eastern Europe and in the former Soviet Union the use of phages continued therapeutically together with or instead of antibiotics. (Sulakvelidze.,et.al,2001)Phage therapy PharmacokineticsPharmacology is the study of medicines impact on the body and bodys impact on the doses.These two ideas are known as pharmacodynamics and pharmacokinetics. In the concept of body, while considering anti microbial as drugs which includes both normal body tissues and the numerous symbiotic micro-organisms. Here we consider only pharmacokinetic aspect of phage therapy pharmacology.Pharmacokinectics describes drugs potential that are sufficient to achieve primary pharmacodynamic effects. This description is distinguished into absorption, distribution, metabolism and excretion components. Drug driving force into the blood is absorption, drug movement into other body tissues is distribution, modification of drugs within the body is metabolism, and movement of drugs out of the body is excretion. These four pharmacokinetic aspects have the effect of both reducing and increasing drug densities. In the case of absorption and distribution, drug densities declines collectable to drug dilution and at the same time drug density gains in specific body compartments. transfiguration results phage inactivation due to phage interaction with immune systems or activation such as phage in situ replication. Excretion can repress of drug densities in the body, it can also increased drug densities in bladder with therapeutic benefits.The success of phage therapy depends on generation of sufficient phage densities in the vicinity of the target bacteria to ca use bacterial removal from the body at some adequate rate. Sufficient densities of phage will increase either to in situ replication which is a active treatment, or a consequence of what can be described as pharmacologically conventional dosing, is called passive treatment. (Abedon et al,2011)Potential benefitsPhage therapy offers a possible alternative to conventional antibiotic treatments for bacterial infections.Phages are very specific to target one or a few strains of bacteria. Traditional antibiotics kill both harmful bacteria and reusable bacteria such as those facilitating food digestion. The specificity of phages might reduce the chance that useful bacteria are killed when fighting on infection. Phages have ability to travel to a required site including brain. (Wikipedia.org)Phages are natural antimicrobial agents to fight bacterial infections in humans, in animals or in crops of agricultural importance. Phages have hygiene measure in hospitals and in food production faci lities. (Brussow Harald)Alternatives to antibioticsPhage is a workable alternative to antibiotics. The collapse of antibiotics and emergence of harmful and drug resistant bacteria, phage therapy starts again and is being reintroduced.Phage therapy has many potential applications in human medicine, ex-serviceman science and agriculture.Specificity Phages are more specific than antibiotics, means one phage will only attack and eat one particular bacteria and no other. Each infection needs a particular phage to treat it. To improve the chances of success phage mixtures are applied or samples can be taken and an appropriate phage identified and grown.Phages can be chosen to be indirectly harmless not only to the host organism, but also to other beneficial bacteria, such as gut flora, thus reduce the chances of infections. Phage therapy give rise to few side effects.Phages replicates inside the patient, a smaller effective dose may not even be necessary.Currently phages are used thera peutically to treat bacterial infections that do not respond to conventional antibiotics particularly in Russia and Georgia. (Prof. Kieth)Need to study PhagesAs we saw research on phages and a lack of knowledge on phage biological science affects on clinical failure.The emergence of antibiotics wiped out further research on medical use of phages. After many years, a new problem of bacterial resistance to use of antibiotic has arisen.Bacteria become resistant to drug used in modern medicine by adapting themselves. Problems created in treating patients in hospitals due to the emergence of modified pathogens such as S.aureus, P. aeruginosa, Acinetobacter baumannii and Mycobacterium tuberculosis.Time required to produce new antibiotic is much larger than the time of bacterial adaptation.therapeutic Uses of Phages and AntibioticsConclusionFor phage therapy multidrug resistant bacteria have opened a second window. (Carlton,1999)Phage therapy is the therapeutic use of lytic phages to trea t bacterial infections. It is an alternative to antibiotics developed for clinical use. Phages are more specific than antibiotics that are in clinical use. This therapy is harmless to eukaryotic hosts undergoing therapy and should not affect normal beneficial flora of the host. theoretically a single small dose is effective.Specificity is the disadvantage because specific phage will only kill a bacterium if it is a match to the specific subspecies. Thus, to improve the chances of success, phage mixture may be applied or clinical samples can be taken and suitable phage identified and grown.In the country of Georgia phages are used to treat bacterial infections therapeutically. (Todar Kenneth)