How viruses infect bacteria?
- E.V. Orlova
- Birkbeck, University of London
Discover the world's research
- 15+ million members
- 118+ million publications
- 700k+ research projects
Join for free
- More than rotating flagella: LPS as a secondary receptor for flagellotropic phage 7-7-1Article
- Jul 2018
- J BACTERIOL
Bacteriophage 7-7-1, a member of the Myoviridae family, infects the soil bacterium Agrobacterium sp. H13-3. Infection requires attachment to actively rotating bacterial flagellar filaments, with flagellar number, length, and rotation speed being important determinants for infection efficiency. To identify secondary receptor(s) on the cell surface, we isolated motile, phage-resistant Agrobacterium sp. H13-3 transposon mutants. Transposon insertion sites were pinpointed using arbitrary-primed polymerase chain reaction and bioinformatics analyses. Three genes were recognized, whose corresponding proteins had the following computationally predicted functions: AGROH133_07337, a glycosyl transferase, AGROH133_13050, a UDP-glucose 4-epimerase, and AGROH133_08824, an integral cytoplasmic membrane protein. The first two gene products are part of the lipopolysaccharide (LPS) synthesis pathway, while the latter is predicted to be a relatively small (13.4 kDa) cytosolic membrane protein with up to four transmembrane helices. Phenotypes of transposon mutants were verified by complementation and site-directed mutagenesis. Additional characterization of motile, phage resistant mutants is also described. Given these findings, we propose a model for Agrobacterium sp. H13-3 infection by bacteriophage 7-7-1 where the phage initially attaches to the flagellar filament and is propelled down towards the cell surface by clockwise flagellar rotation. The phage then attaches to and degrades the LPS to reach the outer membrane, and ejects its DNA into the host using its syringe-like contractile tail. We hypothesize that the integral membrane protein plays an important role in events following viral DNA ejection or in LPS processing and/or deployment. The proposed two-step attachment mechanism may be conserved among other flagellotropic phages infecting Gram-negative bacteria.
Richard F Helm
Flagellotropic bacteriophages belong to tailed phage order Caudovirales, which are the most abundant in the virome. While it is known that these viruses adhere to the bacterial flagellum and use flagellar rotation to reach the cell surface, their infection mechanisms are poorly understood. Characterizing flagellotropic phage-host interactions is crucial to understanding how microbial communities are shaped. Using a transposon mutagenesis approach combined with a screen for motile, phage-resistant mutants, we identified lipopolysaccharides as the secondary cell surface receptor for phage 7-7-1. This is the first cell surface receptor identified for flagellotropic phages. One hypothetical membrane protein was also recognized as essential for infection. These new findings, together with previous results, culminated in an infection model for phage 7-7-1.
- … Apart from antibiotic resistance, several other reasons have driven the scientists to give a renewed attention to bacteriophages. For example, a viral genome is constantly seen within multidrug resistant (MDR) bacterial DNA indicating that these viruses can still recognize and infect these bacteria despite their antibiotic resistance . Evidence from ecological studies revealed that each bacterial species in the environment can be infected by more than 10 phage species suggesting that these viruses playing critical roles in shaping the nutrient cycling and evolutionary dynamics of the organisms they infect . …Inhibitory Effect of Bacteriophages Isolated from Sewage Water in the City of Kirkuk on some Types of Human Pathogenic BacteriaArticleFull-text available
- Dec 2017
Most approaches to combat antibiotic resistant bacteria concentrate on discovering new antibiotics or modifying existing ones. However, one of the most promising alternatives is the use of bacteriophages. This study was focused on the isolation of bacteriophages that are specific to some of commonly human pathogens namely E. coli, Streptococcus pyogenes, Staphylococcus aureus, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella spp. and Klebsiella pneumoniae. These bacteriophages were isolated from sewages that were collected from four different locations in Kirkuk City. Apart from S. pyogenes, bacteriophages specific to all tested bacteria were successfully isolated and tested for their effectiveness by spot test. The most effective bacteriophages that were isolated from sewages and sewage water of Al-Jumhori Hospital compared to other sites. It is concluded that the sewage water of hospitals represents a perfect environment for these bacteriophages.
Alaa Ty Al-Hammadi
- Marine polysaccharides: therapeutic efficacy and biomedical applicationsArticle
- Sep 2017
- ARCH PHARM RES
The ocean contains numerous marine organisms, including algae, animals, and plants, from which diverse marine polysaccharides with useful physicochemical and biological properties can be extracted. In particular, fucoidan, carrageenan, alginate, and chitosan have been extensively investigated in pharmaceutical and biomedical fields owing to their desirable characteristics, such as biocompatibility, biodegradability, and bioactivity. Various therapeutic efficacies of marine polysaccharides have been elucidated, including the inhibition of cancer, inflammation, and viral infection. The therapeutic activities of these polysaccharides have been demonstrated in various settings, from in vitro laboratory-scale experiments to clinical trials. In addition, marine polysaccharides have been exploited for tissue engineering, the immobilization of biomolecules, and stent coating. Their ability to detect and respond to external stimuli, such as pH, temperature, and electric fields, has enabled their use in the design of novel drug delivery systems. Thus, along with the promising characteristics of marine polysaccharides, this review will comprehensively detail their various therapeutic, biomedical, and miscellaneous applications.
- Insect symbiotic bacteria harbour viral pathogens for transovarial transmissionArticle
- Mar 2017
Many insects, including mosquitoes, planthoppers, aphids and leafhoppers, are the hosts of bacterial symbionts and the vectors for transmitting viral pathogens1, 2, 3. In general, symbiotic bacteria can indirectly affect viral transmission by enhancing immunity and resistance to viruses in insects3, 4, 5. Whether symbiotic bacteria can directly interact with the virus and mediate its transmission has been unknown. Here, we show that an insect symbiotic bacterium directly harbours a viral pathogen and mediates its transovarial transmission to offspring. We observe rice dwarf virus (a plant reovirus) binding to the envelopes of the bacterium Sulcia, a common obligate symbiont of leafhoppers6, 7, 8, allowing the virus to exploit the ancient oocyte entry path of Sulcia in rice leafhopper vectors. Such virus–bacterium binding is mediated by the specific interaction of the viral capsid protein and the Sulcia outer membrane protein. Treatment with antibiotics or antibodies against Sulcia outer membrane protein interferes with this interaction and strongly prevents viral transmission to insect offspring. This newly discovered virus–bacterium interaction represents the first evidence that a viral pathogen can directly exploit a symbiotic bacterium for its transmission. We believe that such a model of virus–bacterium communication is a common phenomenon in nature.
- Salivary Diagnostics and the Oral MicrobiomeArticleFull-text available
- Jan 2015
Our oral cavity hosts an extraordinary variety of microorganisms. Recent work has started to look at the composition of the oral microbiome in both healthy and disease states. Various stages of caries, gingivitis, and periodontitis, plus novel work understanding the role of bacteria in other diseases/conditions and carcinogenesis, reveal that our oral microbiome has an intriguing link to our global health. Together, these studies have combined a number of techniques, including human oral microbe identifi cation microarray (HOMIM) and high-throughput sequencing, to survey the oral fl ora composition. Microorganisms' sensitivity to small changes in the environment including pH, nutrients and metabolites, oxygen and water levels, and host immune factors has been broadly studied. Ideally, the high sensitivity of oral microorganisms should forecast subtle changes in the health status and potentially serve as a biomarker for early detection of disease. Paired with other host saliva biomarkers, the oral microbiome presents a novel noninvasive diagnostic tool for monitoring changes in human physiology and a potential shift toward disease.
Gena D Tribble
- … Los virus son pequeñas partículas infecciosas, normalmente entre 20-200 nm, consisten en un núcleo de ácido nucleico (de cadena simple o doble, de ARN o ADN) rodeado por una cubierta proteica (cápside) y en algunos casos, una cubierta de lípidos (9); existen en una gran variedad de formas que infectan a prácticamente todas las criaturas vivientes: animales, plantas, insectos y bacterias (10,11); los virus que afectan a estas últimas son conocidos también como bacteriófagos o fagos y se consideran las entidades más abundantes de la biosfera, el número total estimado es de 10 30 a 10 32 y en ambientes acuáticos se encuentran desde 10 4 mL-1 hasta 10 8 mL-1 (12). A pesar de que los fagos son virus simples a nivel estructural y genético, han resultado muy útiles para el estudio de varios fenómenos moleculares; los conocimientos alcanzados en las investigaciones realizadas con fagos constituyeron la base del desarrollo de la biología molecular y el número de la progenie liberada puede llegar hasta 200 nuevas partículas fágicas por bacterias lisadas (13,14,15). …APLICACIÓN DE BACTERIÓFAGOS EN ALIMENTOSArticleFull-text available
Introducción Las enfermedades transmitidas por alimentos (ETA's) son aquellas de carácter infeccioso o tóxico causadas principalmente al consumirse alimentos o bebidas contaminados; la Organización Mundial de la Salud estima que dos millones de personas mueren a causa de enfermedades diarreicas cada año. En 2004, las enfermedades diarreicas fueron la tercera mayor causa de muerte en países de ingresos bajos, donde ocasionaron el 6,9% de los fallecimientos. Son la segunda mayor causa de muerte de niños menores de cinco años, después de la neumonía. La mayoría de las personas que fallecen por enfermedades diarreicas, mueren por una grave deshidratación y pérdida de líquidos (1, 2). Los datos del Centro Nacional de Vigilancia Epidemiológica y de Control de Enfermedades (CENAVECE) indican que en la República Mexicana, entre los problemas de salud más importantes se encuentran los padecimientos gastrointestinales; a nivel nacional las enfermedades infecciosas intestinales se ubican dentro de las primeras 10 causas de mortalidad de niños en edad escolar, en el caso del estado de Nuevo León, éste ha permanecido desde hace 5 años entre los primeros 12 lugares con casos de fiebre tifoidea y en los primeros 20, con casos de fiebre paratifoidea y otras salmonelosis (3). Se define como diarrea a la deposición por tres o más veces al día (o con una frecuencia mayor que la normal para la persona) de heces sueltas o líquidas, suele ser un síntoma de una infección del tracto digestivo, que puede estar ocasionada en su mayoría por diferentes microorganismos como son, bacterias (Bacillus cereus, Salmonella sp, Clostridium botulinum, Vibrio cholera), virus (Norwalk, Rotavirus, Hepatitis A) y parásitos (Entamoeba histolytica, Cryptosporidium parvum, Toxoplasma gondii) que entran al organismo a través del tracto gastrointestinal. La infección se transmite por alimentos o agua de consumo contaminados, o bien de una persona a otra como resultado de una higiene deficiente (4, 5, 6). En las últimas décadas, se han identificado nuevos patógenos importantes que se transmiten a través de los alimentos de los cuales se destacan Escherichia coli O157:H7, Campylobacter jejuni, Enterobacter sakazakii y Listeria monocytogenes (7). Así, también se han identificado nuevos métodos de propagación de estos patógenos, los cambios en las poblaciones, en los estilos de vida de los consumidores y en las preferencias alimentarias han producido cambios en la formulación, manufactura y distribución de los mismos teniendo un impacto sobre la inocuidad de los alimentos. La industria alimentaria ha evolucionado de ser local a aquella en donde la producción y el procesamiento están ubicados en diferentes partes del país y del mundo, estos cambios, aunados a la habilidad que tienen los microorganismos para evolucionar rápidamente y adaptarse a su medio ambiente, presentan nuevos retos microbiológicos a la industria alimentaria (8).
- The tail structure of bacteriophage T4 and its mechanism of contractionArticleFull-text available
- Aug 2005
- Nat Struct Mol Biol
Bacteriophage T4 and related viruses have a contractile tail that serves as an efficient mechanical device for infecting bacteria. A three-dimensional cryo-EM reconstruction of the mature T4 tail assembly at 15-Å resolution shows the hexagonal dome-shaped baseplate, the extended contractile sheath, the long tail fibers attached to the baseplate and the collar formed by six whiskers that interact with the long tail fibers. Comparison with the structure of the contracted tail shows that tail contraction is associated with a substantial rearrangement of the domains within the sheath protein and results in shortening of the sheath to about one-third of its original length. During contraction, the tail tube extends beneath the baseplate by about one-half of its total length and rotates by 345°, allowing it to cross the host's periplasmic space.
Victor A Kostyuchenko
Michael G. Rossmann
- The tail sheath structure of bacteriophage T4: A molecular machine for infecting bacteriaArticleFull-text available
- Mar 2009
- EMBO J
The contractile tail of bacteriophage T4 is a molecular machine that facilitates very high viral infection efficiency. Its major component is a tail sheath, which contracts during infection to less than half of its initial length. The sheath consists of 138 copies of the tail sheath protein, gene product (gp) 18, which surrounds the central non-contractile tail tube. The contraction of the sheath drives the tail tube through the outer membrane, creating a channel for the viral genome delivery. A crystal structure of about three quarters of gp18 has been determined and was fitted into cryo-electron microscopy reconstructions of the tail sheath before and after contraction. It was shown that during contraction, gp18 subunits slide over each other with no apparent change in their structure.
Lidia Petrovna Kurochkina
Michael G. Rossmann
- Bacteriophage Lambda Stabilization by Auxiliary Protein gpD: Timing, Location, and Mechanism of Attachment Determined by Cryo-EMArticle
- Oct 2008
We report the cryo-EM structure of bacteriophage lambda and the mechanism for stabilizing the 20-A-thick capsid containing the dsDNA genome. The crystal structure of the HK97 bacteriophage capsid fits most of the T = 7 lambda particle density with only minor adjustment. A prominent surface feature at the 3-fold axes corresponds to the cementing protein gpD, which is necessary for stabilization of the capsid shell. Its position coincides with the location of the covalent cross-link formed in the docked HK97 crystal structure, suggesting an evolutionary replacement of this gene product in lambda by autocatalytic chemistry in HK97. The crystal structure of the trimeric gpD, in which the 14 N-terminal residues required for capsid binding are disordered, fits precisely into the corresponding EM density. The N-terminal residues of gpD are well ordered in the cryo-EM density, adding a strand to a beta-sheet formed by the capsid proteins and explaining the mechanism of particle stabilization.
John E Johnson
Gabriel C Lander
- Classification of Vibrio BacteriophagesArticle
- Feb 1984
85 Vibrio phages, 84 of them tailed and 1 filamentous, were surveyed. The tailed phages belonged to six basic morphotypes and to the Myoviridae, Siphoviridae, or Podoviridae families. 63 phages were classified into 18 species. The filamentous phage is a member of the Inovirus genus of the Inoviridae family. Vibrio phages are very heterogenous and include some morphologically interesting viruses. Several Vibrio phages closely resemble phages of other gram-negative bacteria, possibly indicating phylogenetic relationships between their hosts.
S S Kasatiya
- Structure and morphogenesis of bacteriophage T4ArticleFull-text available
- Dec 2003
- CELL MOL LIFE SCI
Bacteriophage T4 is one of the most complex viruses. More than 40 different proteins form the mature virion, which consists of a protein shell encapsidating a 172-kbp double-stranded genomic DNA, a 'tail,' and fibers, attached to the distal end of the tail. The fibers and the tail carry the host cell recognition sensors and are required for attachment of the phage to the cell surface. The tail also serves as a channel for delivery of the phage DNA from the head into the host cell cytoplasm. The tail is attached to the unique 'portal' vertex of the head through which the phage DNA is packaged during head assembly. Similar to other phages, and also herpes viruses, the unique vertex is occupied by a dodecameric portal protein, which is involved in DNA packaging.
Vadim V Mesyanzhinov
Michael G. Rossmann
- Three-Dimensional Rearrangement of Proteins in the Tail of Bacteriophage T4 on Infection of Its HostArticle
- Sep 2004
The contractile tail of bacteriophage T4 undergoes major structural transitions when the virus attaches to the host cell surface. The baseplate at the distal end of the tail changes from a hexagonal to a star shape. This causes the sheath around the tail tube to contract and the tail tube to protrude from the baseplate and pierce the outer cell membrane and the cell wall before reaching the inner cell membrane for subsequent viral DNA injection. Analogously, the T4 tail can be contracted by treatment with 3 M urea. The structure of the T4 contracted tail, including the head-tail joining region, has been determined by cryo-electron microscopy to 17 A resolution. This 1200 A-long, 20 MDa structure has been interpreted in terms of multiple copies of its approximately 20 component proteins. A comparison with the metastable hexagonal baseplate of the mature virus shows that the baseplate proteins move as rigid bodies relative to each other during the structural change.
Victor A Kostyuchenko
Michael G. Rossmann
- Structure of epsilon15 bacteriophage reveals genome organization and DNA packaging/injection apparatusArticleFull-text available
- Mar 2006
The critical viral components for packaging DNA, recognizing and binding to host cells, and injecting the condensed DNA into the host are organized at a single vertex of many icosahedral viruses. These component structures do not share icosahedral symmetry and cannot be resolved using a conventional icosahedral averaging method. Here we report the structure of the entire infectious Salmonella bacteriophage epsilon15 (ref. 1) determined from single-particle cryo-electron microscopy, without icosahedral averaging. This structure displays not only the icosahedral shell of 60 hexamers and 11 pentamers, but also the non-icosahedral components at one pentameric vertex. The densities at this vertex can be identified as the 12-subunit portal complex sandwiched between an internal cylindrical core and an external tail hub connecting to six projecting trimeric tailspikes. The viral genome is packed as coaxial coils in at least three outer layers with approximately 90 terminal nucleotides extending through the protein core and the portal complex and poised for injection. The shell protein from icosahedral reconstruction at higher resolution exhibits a similar fold to that of other double-stranded DNA viruses including herpesvirus, suggesting a common ancestor among these diverse viruses. The image reconstruction approach should be applicable to studying other biological nanomachines with components of mixed symmetries.
- Classification of bacteriophages
- Ackermann H-W
- Ackermann H-W
- 15+ million members
- 118+ million publications
- 700k+ research projects
Join for free
Structural study of the BPV E1 helicase/DNA complex
Cyril M Sanders
Bacteriophages and Their Structural Organisation
are able to pass through fine porcelain filters. They exist in a huge variety of forms and
infect practically all living systems: animals, plants, insects and bacteria. All viruses have a
genome, typically only one type of nucleic acid, but it could be one or several molecules of
DNA or RNA, … [Show full abstract] which is surrounded by a protective stable coat (capsid) and sometimes by
additional layers which may be very complex and contain carbohydrates, lipids, and
additional proteins. The viruses that have only a protein coat are named “naked”, or non-
enveloped viruses. Many viruses have an envelope (enveloped viruses) that wraps around
the protein capsid. This envelope is formed from a lipid membrane of the host cell during
the release of a virus out of the cell.
Structure and function of bacteriophage T4
- Michael G. Rossmann
Moh Lan Yap
Structural Conservation of the Myoviridae Phage Tail Sheath Protein Fold
Lidia Petrovna Kurochkina
- Andrei Fokine
- Michael G. Rossmann
Morphogenesis of the T4 tail and tail fibers
Mark Johan van Raaij
- Michael G. Rossmann
Jump to navigation
Jump to search
The structure of a typical myovirus bacteriophage
Anatomy and infection cycle of phage T4
A bacteriophage ( // ), also known informally as a phage ( // ), is a virus that infects and replicates within Bacteria and Archaea . The term was derived from “bacteria” and the Greek φαγεῖν (phagein), “to devour”. Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome , and may have relatively simple or elaborate structures. Their genomes may encode as few as four genes and as many as hundreds of genes . Phages replicate within the bacterium following the injection of their genome into its cytoplasm . Bacteriophages are among the most common and diverse entities in the biosphere .  Bacteriophages are ubiquitous viruses, found wherever bacteria exist. It is estimated there are more than 1031 bacteriophages on the planet, more than every other organism on Earth, including bacteria, combined. 
Phages are widely distributed in locations populated by bacterial hosts, such as soil or the intestines of animals. One of the densest natural sources for phages and other viruses is seawater, where up to 9×108 virions per millilitre have been found in microbial mats at the surface,  and up to 70% of marine bacteria may be infected by phages.  They have been used for over 90 years as an alternative to antibiotics in the former Soviet Union and Central Europe as well as in France.  They are seen as a possible therapy against multi-drug-resistant strains of many bacteria (see phage therapy ).  Nevertheless, phages of Inoviridae have been shown to complicate biofilms involved in pneumonia and cystic fibrosis and shelter the bacteria from drugs meant to eradicate disease, thus promote persistent infection. 
- 1 Classification
- 2 History
- 3 Uses
- 3.1 Phage therapy
- 3.2 Dairy industry
- 3.3 Other
- 4 Replication
- 4.1 Attachment and penetration
- 4.2 Synthesis of proteins and nucleic acid
- 4.3 Virion assembly
- 4.4 Release of virions
- 5 Genome structure
- 6 Systems biology
- 7 In the environment
- 8 Model bacteriophages
- 9 See also
- 10 References
- 11 External links
Classification[ edit ]
Bacteriophages occur abundantly in the biosphere, with different genomes, and lifestyles. Phages are classified by the International Committee on Taxonomy of Viruses (ICTV) according to morphology and nucleic acid.
Nineteen families are currently recognized by the ICTV that infect bacteria and archaea . Of these, only two families have RNA genomes, and only five families are surrounded by an envelope. Of the viral families with DNA genomes, only two have single-stranded genomes. Eight of the viral families with DNA genomes have circular genomes while nine have linear genomes. Nine families infect bacteria only, nine infect archaea only, and one (Tectiviridae) infects both bacteria and archaea.
Bacteriophage P22, a member of the Podoviridae by morphology due to its short, non-contractile tail
|Caudovirales||Myoviridae||Non enveloped , contractile tail||Linear dsDNA||T4 phage , Mu , PBSX, P1Puna-like, P2, I3, Bcep 1, Bcep 43, Bcep 78|
|Siphoviridae||Nonenveloped, noncontractile tail (long)||Linear dsDNA||λ phage , T5 phage , phi, C2, L5, HK97 , N15|
|Podoviridae||Nonenveloped, noncontractile tail (short)||Linear dsDNA||T7 phage , T3 phage , Φ29 , P22, P37|
|Ligamenvirales||Lipothrixviridae||Enveloped, rod-shaped||Linear dsDNA||Acidianus filamentous virus 1|
|Rudiviridae||Nonenveloped, rod-shaped||Linear dsDNA||Sulfolobus islandicus rod-shaped virus 1|
|Unassigned||Ampullaviridae||Enveloped, bottle-shaped||Linear dsDNA|
|Bicaudaviridae||Nonenveloped, lemon-shaped||Circular dsDNA|
|Clavaviridae||Nonenveloped, rod-shaped||Circular dsDNA|
|Corticoviridae||Nonenveloped, isometric||Circular dsDNA|
|Cystoviridae||Enveloped, spherical||Segmented dsRNA|
|Fuselloviridae||Nonenveloped, lemon-shaped||Circular dsDNA|
|Globuloviridae||Enveloped, isometric||Linear dsDNA|
|Guttaviridae||Nonenveloped, ovoid||Circular dsDNA|
|Inoviridae||Nonenveloped, filamentous||Circular ssDNA||M13|
|Leviviridae||Nonenveloped, isometric||Linear ssRNA||MS2 , Qβ|
|Microviridae||Nonenveloped, isometric||Circular ssDNA||ΦX174|
|Plasmaviridae||Enveloped, pleomorphic||Circular dsDNA|
|Tectiviridae||Nonenveloped, isometric||Linear dsDNA|
History[ edit ]
In 1896, Ernest Hanbury Hankin reported that something in the waters of the Ganges and Yamuna rivers in India had marked antibacterial action against cholera and could pass through a very fine porcelain filter.  In 1915, British bacteriologist Frederick Twort , superintendent of the Brown Institution of London, discovered a small agent that infected and killed bacteria. He believed the agent must be one of the following:
- a stage in the life cycle of the bacteria;
- an enzyme produced by the bacteria themselves; or
- a virus that grew on and destroyed the bacteria. 
Twort’s work was interrupted by the onset of World War I and shortage of funding. Independently, French-Canadian microbiologist Félix d’Hérelle , working at the Pasteur Institute in Paris , announced on 3 September 1917, that he had discovered “an invisible, antagonistic microbe of the dysentery bacillus”. For d’Hérelle, there was no question as to the nature of his discovery: “In a flash I had understood: what caused my clear spots was in fact an invisible microbe … a virus parasitic on bacteria.”  D’Hérelle called the virus a bacteriophage or bacteria-eater (from the Greek phagein meaning “to devour”). He also recorded a dramatic account of a man suffering from dysentery who was restored to good health by the bacteriophages.  It was D’Herelle who conducted much research into bacteriophages and introduced the concept of phage therapy . 
In 1969, Max Delbrück , Alfred Hershey and Salvador Luria were awarded the Nobel Prize in Physiology or Medicine for their discoveries of the replication of viruses and their genetic structure. 
Uses[ edit ]
Phage therapy[ edit ]
Phages were discovered to be antibacterial agents and were used in the former Soviet Republic of Georgia (pioneered there by Giorgi Eliava with help from the co-discoverer of bacteriophages, Félix d’Herelle ) during the 1920s and 1930s for treating bacterial infections. 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. 
- Publication of research in the Soviet Union was mainly in the Russian or Georgian languages and were not followed internationally for many years.
The use of phages has continued since the end of the Cold War in Georgia and elsewhere in Central and Eastern Europe. The first regulated, randomized, double-blind clinical trial was reported in the Journal of Wound Care in June 2009, which evaluated the safety and efficacy of a bacteriophage cocktail to treat infected venous ulcers of the leg in human patients.  The FDA approved the study as a Phase I clinical trial. The study’s results demonstrated the safety of therapeutic application of bacteriophages but did not show efficacy. The authors explain that the use of certain chemicals that are part of standard wound care (e.g. lactoferrin or silver) may have interfered with bacteriophage viability.  Another controlled clinical trial in Western Europe (treatment of ear infections caused by Pseudomonas aeruginosa) was reported shortly after this in the journal Clinical Otolaryngology in August 2009.  The study concludes that bacteriophage preparations were safe and effective for treatment of chronic ear infections in humans. 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.  Meanwhile, bacteriophage researchers are developing engineered viruses to overcome antibiotic resistance , and engineering the phage genes responsible for coding enzymes which degrade the biofilm matrix, phage structural proteins and also the enzymes responsible for lysis of the bacterial cell wall.    There have been results showing that T4 phages that are small in size and short-tailed can be helpful in detecting E.coli in the human body. 
D’Herelle “quickly learned that bacteriophages are found wherever bacteria thrive: in sewers, in rivers that catch waste runoff from pipes, and in the stools of convalescent patients.”  This includes rivers traditionally thought to have healing powers, including India’s Ganges River. 
In 2015, a psychology professor whose wife is a professor of public health at University of California, San Diego, became ill with a resistant strain of Acinetobacter baumanii, a deadly strain of bacteria especially prevalent in the Middle East. The psychology professor, Tom Patterson, became ill while traveling in Egypt, and eventually fell into a coma. Patterson’s wife, Steffanie Strathdee , began working with the head of infectious diseases at UCSD. In her search for alternatives to antibiotics, Strathdee had discovered bacteriophages, and concentrated on reaching out to various institutions to find an appropriate treatment for her husband’s infection. According to an article by Laura Kahn in the Bulletin of the Atomic Scientists , “The US Food and Drug Administration (FDA) provided emergency approval for experimental intravenous and intra-abdominal-cavity treatments. The phage cocktail crafted to attack the professor’s infection needed several adjustments, but after three days of treatment in the intensive care unit at Thornton Hospital, part of UC San Diego Health, he woke from his coma.” 
Dairy industry[ edit ]
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. 
Other[ edit ]
Food industry. Since 2006, the United States Food and Drug Administration (FDA) and United States Department of Agriculture (USDA) have approved several bacteriophage products. LMP-102 (Intralytix) was approved for treating ready-to-eat (RTE) poultry and meat products. In that same year, the FDA approved LISTEX (developed and produced by Micreos ) using bacteriophages on cheese to kill Listeria monocytogenes bacteria, giving them generally recognized as safe (GRAS) status.  In July 2007, the same bacteriophage were approved for use on all food products.  In 2011 USDA confirmed that LISTEX is a clean label processing aid and is included in USDA.  Research in the field of food safety is continuing to see if lytic phages are a viable option to control other food-borne pathogens in various food products.
Diagnostics. In 2011, the FDA cleared the first bacteriophage-based product for in vitro diagnostic use.  The KeyPath MRSA/MSSA Blood Culture Test uses a cocktail of bacteriophage to detect Staphylococcus aureus in positive blood cultures and determine methicillin resistance or susceptibility. The test returns results in about 5 hours, compared to 2–3 days for standard microbial identification and susceptibility test methods. It was the first accelerated antibiotic susceptibility test approved by the FDA. 
Counteracting bioweapons and toxins. Government agencies in the West have for several years been looking to Georgia and the former Soviet Union for help with exploiting phages for counteracting bioweapons and toxins, such as anthrax and botulism .  Developments are continuing among research groups in the US. 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.g., in hospitals, and as preventative treatments for catheters and medical devices before use in clinical settings. The technology for phages to be applied to dry surfaces, e.g., uniforms, curtains, or even sutures for surgery now exists. Clinical trials reported in Clinical Otolaryngology  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. 
Phage display is a different use of phages involving a library of phages with a variable peptide linked to a surface protein. Each phage’s 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 can be selected through their binding affinity to an immobilized molecule (e.g., botulism toxin) to neutralize it. 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. 
Antimicrobial drug discovery. Phage proteins often have antimicrobial activity and may serve as leads for peptidomimetics , i.e. drugs that mimic peptides.  Phage-ligand technology makes use of phage proteins for various applications such as binding of bacteria and bacterial components (e.g. endotoxin ) and lysis of bacteria. 
Basic research. Bacteriophages are also important model organisms for studying principles of evolution and ecology . 
Replication[ edit ]
Diagram of the DNA injection process
Bacteriophages may have a lytic cycle or a lysogenic cycle , and a few viruses are capable of carrying out both. 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 is usually 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 of the cell’s offspring.
An example of a bacteriophage known to follow the lysogenic cycle and the lytic cycle is the phage lambda of E. coli. 
Sometimes prophages may provide benefits to the host bacterium while they are dormant by adding new functions to the bacterial genome in a phenomenon called lysogenic conversion . Examples are the conversion of harmless strains of Corynebacterium diphtheriae or Vibrio cholerae by bacteriophages to highly virulent ones, which cause diphtheria or cholera , respectively.   Strategies to combat certain bacterial infections by targeting these toxin-encoding prophages have been proposed. 
Attachment and penetration[ edit ]
In this electron micrograph of bacteriophages attached to a bacterial cell, the viruses are the size and shape of coliphage T1.
To enter a host cell, bacteriophages attach to specific receptors on the surface of bacteria, including lipopolysaccharides , teichoic acids , proteins , or even flagella . This specificity means a bacteriophage can infect only certain bacteria bearing receptors to which they can bind, which in turn determines the phage’s host range. Host growth conditions also influence the ability of the phage to attach and invade them.  As phage virions do not move independently, they must rely on random encounters with the right receptors when in solution (blood, lymphatic circulation, irrigation, soil water, etc.).
Myovirus bacteriophages use a hypodermic syringe -like motion to inject their genetic material into the cell. After making contact with 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,  injecting genetic material through the bacterial membrane. The injection is done 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 similar to that of a myovirus, so they instead 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. For RNA-based phages, RNA replicase is synthesized early in the process. Proteins modify the bacterial RNA polymerase so it preferentially transcribes viral mRNA. The host’s normal synthesis of proteins and nucleic acids is disrupted, and it is forced to manufacture viral products instead. These products go on to become part of new virions within the cell, helper proteins that help assemble the new virions, or proteins involved in cell lysis . Walter Fiers ( University of Ghent , Belgium ) was the first to establish the complete nucleotide sequence of a gene (1972) and of the viral genome of bacteriophage MS2 (1976). 
Virion assembly[ edit ]
In the case of the T4 phage , the construction of new virus particles involves the assistance of helper proteins. 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.
Diagram of a typical tailed bacteriophage structure
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 phages , 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 .
Genome structure[ edit ]
Given the millions of different phages in the environment, phages’ genomes come in a variety of forms and sizes. RNA phage such as MS2 have the smallest genomes of only a few kilobases. However, some DNA phages 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. 
Bacteriophage genomes can be highly mosaic , i.e. the genome of many phage species appear to be composed of numerous individual modules. 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).  Evolutionary mechanisms shaping the genomes of bacterial viruses vary between different families and depend on the type of the nucleic acid, characteristics of the virion structure, as well as the mode of the viral life cycle. 
Systems biology[ edit ]
Phages often have dramatic effects on their hosts. As a consequence, the transcription pattern of the infected bacterium may change considerably. For instance, infection of Pseudomonas aeruginosa by the temperate phage PaP3 changed the expression of 38% (2160/5633) of its host’s genes. Many of these effects are probably indirect, hence the challenge becomes to identify the direct interactions among bacteria and phage. 
Several attempts have been made to map Protein–protein interactions among phage and their host. For instance, bacteriophage lambda was found to interact with its host E. coli by 31 interactions. 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 are most likely several key interactions and many indirect interactions whose role remains uncharacterized. 
In the environment[ edit ]
Metagenomics has allowed the in-water detection of bacteriophages that was not possible previously. 
Bacteriophages have also been used in hydrological tracing and modelling in river systems, especially where surface water and groundwater interactions occur. 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.  Non-polluted water may contain ca. 2×108 bacteriophages per mL. 
Bacteriophages are thought to extensively contribute to horizontal gene transfer in natural environments, principally via transduction but also via transformation .  Metagenomics -based studies have also revealed that viromes from a variety of environments harbor antibiotic resistance genes, including those that could confer multidrug resistance . 
Model bacteriophages[ edit ]
The following bacteriophages are extensively studied:
- 186 phage
- λ phage
- Φ6 phage
- Φ29 phage
- G4 phage
- M13 phage
- MS2 phage (23–28 nm in size  )
- N4 phage
- P1 phage
- P2 phage
- P4 phage
- R17 phage
- T2 phage
- T4 phage (169 kbp genome,  200 nm long  )
- T7 phage
- T12 phage
See also[ edit ]
- DNA viruses
- Phage ecology
- Phage monographs (a comprehensive listing of phage and phage-associated monographs, 1921 – present)
- RNA viruses
References[ edit ]
- ^ a b Mc Grath S and van Sinderen D (editors). (2007). Bacteriophage: Genetics and Molecular Biology (1st ed.). Caister Academic Press. ISBN 978-1-904455-14-1 .  .
- ^ “Novel Phage Therapy Saves Patient with Multidrug-Resistant Bacterial Infection” . UC Health – UC San Diego. Retrieved 2018-05-13.
- ^ a b Wommack, K. E.; Colwell, R. R. (2000). “Virioplankton: Viruses in Aquatic Ecosystems” . Microbiology and Molecular Biology Reviews. 64 (1): 69–114. doi : 10.1128/MMBR.64.1.69-114.2000 . PMC 98987 . PMID 10704475 .
- ^ a b c Prescott, L. (1993). Microbiology, Wm. C. Brown Publishers, ISBN 0-697-01372-3
- ^ a b BBC Horizon (1997): The Virus that Cures – Documentary about the history of phage medicine in Russia and the West
- ^ Keen, E. C. (2012). “Phage Therapy: Concept to Cure” . Frontiers in Microbiology. 3: 238. doi : 10.3389/fmicb.2012.00238 . PMC 3400130 . PMID 22833738 .
- ^ “Bacteria and bacteriophages collude in the formation of clinically frustrating biofilms” .
- ^ Hankin E H. (1896). “L’action bactericide des eaux de la Jumna et du Gange sur le vibrion du cholera” . Annales de l’Institut Pasteur (in French). 10: 511–523.
- ^ Twort, F. W. (1915). “An Investigation on the Nature of Ultra-Microscopic Viruses”. The Lancet. 186 (4814): 1241–1243. doi : 10.1016/S0140-6736(01)20383-3 .
- ^ Félix d’Hérelles (1917). “Sur un microbe invisible antagoniste des bacilles dysentériques” (PDF). Comptes Rendus de l’Académie des Sciences de Paris. 165: 373–5. Archived (PDF) from the original on 4 December 2010. Retrieved 5 September 2010.
- ^ Félix d’Hérelle (1949). “The bacteriophage” (PDF). Science News. 14: 44–59. Retrieved 5 September 2010.
- ^ Keen EC (2012). “Felix d’Herelle and Our Microbial Future”. Future Microbiology. 7 (12): 1337–1339. doi : 10.2217/fmb.12.115 . PMID 23231482 .
- ^ “The Nobel Prize in Physiology or Medicine 1969” . Nobel Foundation. Retrieved 2007-07-28.
- ^ Kutter, Elizabeth; De Vos, Daniel; Gvasalia, Guram; Alavidze, Zemphira; Gogokhia, Lasha; Kuhl, Sarah; Abedon, Stephen (1 January 2010). “Phage Therapy in Clinical Practice: Treatment of Human Infections”. Current Pharmaceutical Biotechnology. 11 (1): 69–86. doi : 10.2174/138920110790725401 . PMID 20214609 .
- ^ a b Rhoads, DD; Wolcott, RD; Kuskowski, MA; Wolcott, BM; Ward, LS; Sulakvelidze, A (June 2009). “Bacteriophage therapy of venous leg ulcers in humans: results of a phase I safety trial”. Journal of Wound Care. 18 (6): 237–8, 240–3. doi : 10.12968/jowc.2009.18.6.42801 . PMID 19661847 .
- ^ Wright, A.; Hawkins, C.H.; Änggård, E.E.; Harper, D.R. (August 2009). “A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy”. Clinical Otolaryngology. 34 (4): 349–357. doi : 10.1111/j.1749-4486.2009.01973.x . PMID 19673983 .
- ^ Wright, A; Hawkins, CH; Anggård, EE; Harper, DR (August 2009). “A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy”. Clinical Otolaryngology. 34 (4): 349–57. doi : 10.1111/j.1749-4486.2009.01973.x . PMID 19673983 .
- ^ Tawil, Nancy (April 2012). “Surface plasmon resonance detection of E. coli and mathicillin-resistant S. aureus bacteriophages” . PLOS Genetics. 3 (5): e78. doi : 10.1371/journal.pgen.0030078 . PMC 1877875 . PMID 17530925 .
- ^ Kuchment, Anna (2012), The Forgotten Cure: The past and future of phage therapy, Springer, p. 11, ISBN 978-1-4614-0250-3
- ^ Deresinski, Stan (15 April 2009). “Bacteriophage Therapy: Exploiting Smaller Fleas” (PDF). Clinical Infectious Diseases. 48 (8): 1096–1101. doi : 10.1086/597405 . PMID 19275495 .
- ^ Kahn, Laura (October 9, 2018). “Bacteriophages: a promising approach to fighting antibiotic-resistant bacteria” . Bulletin of the Atomic Scientists.
- ^ Atamer, Zeynep; Samtlebe, Meike; Neve, Horst; J. Heller, Knut; Hinrichs, Joerg (2013-07-16). “Review: elimination of bacteriophages in whey and whey products” . Frontiers in Microbiology. 4: 191. doi : 10.3389/fmicb.2013.00191 . ISSN 1664-302X . PMC 3712493 . PMID 23882262 .
- ^ U.S. FDA/CFSAN: Agency Response Letter, GRAS Notice No. 000198
- ^ (U.S. FDA/CFSAN: Agency Response Letter, GRAS Notice No. 000218)
- ^ FSIS Directive 7120 Archived 18 October 2011 at the Wayback Machine .
- ^ FDA 510(k) Premarket Notification
- ^ 
- ^ The New York Times: Studying anthrax in a Soviet-era lab – with Western funding
- ^ Wright, A.; Hawkins, C.; Anggård, E.; Harper, D. (2009). “A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy”. Clinical Otolaryngology. 34 (4): 349–357. doi : 10.1111/j.1749-4486.2009.01973.x . PMID 19673983 .
- ^ Dobozi-King, M.; Seo, S.; Kim, J.U.; Young, R.; Cheng, M.; Kish, L.B. (2005). “Rapid detection and identification of bacteria: SEnsing of Phage-Triggered Ion Cascade (SEPTIC)” (PDF). Journal of Biological Physics and Chemistry. 5: 3–7.
- ^ Smith GP, Petrenko VA (April 1997). “Phage Display”. Chem. Rev. 97 (2): 391–410. doi : 10.1021/cr960065d . PMID 11848876 .
- ^ Liu, Jing; Dehbi, Mohammed; Moeck, Greg; Arhin, Francis; Bauda, Pascale; Bergeron, Dominique; Callejo, Mario; Ferretti, Vincent; Ha, Nhuan (February 2004). “Antimicrobial drug discovery through bacteriophage genomics”. Nature Biotechnology. 22 (2): 185–191. doi : 10.1038/nbt932 . ISSN 1087-0156 . PMID 14716317 .
- ^ Technological background Phage-ligand technology
- ^ Keen, E. C. (2014). “Tradeoffs in bacteriophage life histories” . Bacteriophage. 4 (1): e28365. doi : 10.4161/bact.28365 . PMC 3942329 . PMID 24616839 .
- ^ Mason, Kenneth A., Jonathan B. Losos, Susan R. Singer, Peter H Raven, and George B. Johnson. (2011). Biology, p. 533. McGraw-Hill, New York. ISBN 978-0-07-893649-4 .
- ^ Mokrousov I (January 2009). “Corynebacterium diphtheriae: genome diversity, population structure and genotyping perspectives”. Infection, Genetics and Evolution. 9 (1): 1–15. doi : 10.1016/j.meegid.2008.09.011 . PMID 19007916 .
- ^ Charles RC, Ryan ET (October 2011). “Cholera in the 21st century”. Current Opinion in Infectious Diseases. 24 (5): 472–7. doi : 10.1097/QCO.0b013e32834a88af . PMID 21799407 .
- ^ Keen, E. C. (December 2012). “Paradigms of pathogenesis: Targeting the mobile genetic elements of disease” . Frontiers in Cellular and Infection Microbiology. 2: 161. doi : 10.3389/fcimb.2012.00161 . PMC 3522046 . PMID 23248780 .
- ^ Gabashvili, I.; Khan, S.; Hayes, S.; Serwer, P. (1997). “Polymorphism of bacteriophage T7”. Journal of Molecular Biology. 273 (3): 658–67. doi : 10.1006/jmbi.1997.1353 . PMID 9356254 .
- ^ Fiers, W.; Contreras, R.; Duerinck, F.; Haegeman, G.; Iserentant, D.; Merregaert, J.; Min Jou, W.; Molemans, F.; Raeymaekers, A.; Van Den Berghe, A.; Volckaert, G.; Ysebaert, M. (1976). “Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene”. Nature. 260 (5551): 500–507. Bibcode : 1976Natur.260..500F . doi : 10.1038/260500a0 . PMID 1264203 .
- ^ Black, LW; Thomas, JA (2012). Condensed genome structure. Advances in Experimental Medicine and Biology. 726. pp. 469–87. doi : 10.1007/978-1-4614-0980-9_21 . ISBN 978-1-4614-0979-3 . PMC 3559133 . PMID 22297527 .
- ^ Morris P, Marinelli LJ, Jacobs-Sera D, Hendrix RW, Hatfull GF (March 2008). “Genomic characterization of mycobacteriophage Giles: evidence for phage acquisition of host DNA by illegitimate recombination” . Journal of Bacteriology. 190 (6): 2172–82. doi : 10.1128/JB.01657-07 . PMC 2258872 . PMID 18178732 .
- ^ Krupovic M, Prangishvili D, Hendrix RW, Bamford DH (December 2011). “Genomics of bacterial and archaeal viruses: dynamics within the prokaryotic virosphere” . Microbiology and Molecular Biology Reviews : MMBR. 75 (4): 610–35. doi : 10.1128/MMBR.00011-11 . PMC 3232739 . PMID 22126996 .
- ^ Zhao X, Chen C, Shen W, Huang G, Le S, Lu S, Li M, Zhao Y, Wang J, Rao X, Li G, Shen M, Guo K, Yang Y, Tan Y, Hu F (2016). “Global Transcriptomic Analysis of Interactions between Pseudomonas aeruginosa and Bacteriophage PaP3” . Sci Rep. 6: 19237. Bibcode : 2016NatSR…619237Z . doi : 10.1038/srep19237 . PMC 4707531 . PMID 26750429 .
- ^ Blasche S, Wuchty S, Rajagopala SV, Uetz P (2013). “The protein interaction network of bacteriophage lambda with its host, Escherichia coli” . J. Virol. 87 (23): 12745–55. doi : 10.1128/JVI.02495-13 . PMC 3838138 . PMID 24049175 .
- ^ Breitbart M, Salamon P, Andresen B, Mahaffy JM, Segall AM, Mead D, Azam F, Rohwer F (October 2002). “Genomic analysis of uncultured marine viral communities” . Proc. Natl. Acad. Sci. U.S.A. 99 (22): 14250–5. doi : 10.1073/pnas.202488399 . PMC 137870 . PMID 12384570 .
- ^ Martin, C. (1988). “The Application of Bacteriophage Tracer Techniques in South West Water”. Water and Environment Journal. 2 (6): 638–642. doi : 10.1111/j.1747-6593.1988.tb01352.x .
- ^ Bergh, O (1989). “HIGH ABUNDANCE OF VIRUSES FOUND IN AQUATIC ENVIRONMENTS” (PDF). Nature. 340 (6233): 467–468. Bibcode : 1989Natur.340..467B . doi : 10.1038/340467a0 . PMID 2755508 . Retrieved 17 November 2015.
- ^ Keen, Eric C.; Bliskovsky, Valery V.; Malagon, Francisco; Baker, James D.; Prince, Jeffrey S.; Klaus, James S.; Adhya, Sankar L.; Groisman, Eduardo A. (2017). “Novel “Superspreader” Bacteriophages Promote Horizontal Gene Transfer by Transformation” . mBio. 8 (1): e02115–16. doi : 10.1128/mBio.02115-16 . ISSN 2150-7511 . PMC 5241400 . PMID 28096488 .
- ^ Lekunberri, Itziar; Subirats, Jessica; Borrego, Carles M.; Balcazar, Jose L. (2017). “Exploring the contribution of bacteriophages to antibiotic resistance”. Environmental Pollution. 220 (Pt B): 981–984. doi : 10.1016/j.envpol.2016.11.059 . ISSN 0269-7491 . PMID 27890586 .
- ^ Strauss, James H.; Sinsheimer, Robert L. (July 1963). “Purification and properties of bacteriophage MS2 and of its ribonucleic acid”. Journal of Molecular Biology. 7 (1): 43–54. doi : 10.1016/S0022-2836(63)80017-0 .
- ^ Miller, ES; Kutter, E; Mosig, G; Arisaka, F; Kunisawa, T; Rüger, W (March 2003). “Bacteriophage T4 genome” . Microbiology and Molecular Biology Reviews : MMBR. 67 (1): 86–156, table of contents. doi : 10.1128/MMBR.67.1.86-156.2003 . PMC 150520 . PMID 12626685 .
- ^ Ackermann, H.-W.; Krisch, H. M. (6 April 2014). “A catalogue of T4-type bacteriophages”. Archives of Virology. 142 (12): 2329–2345. doi : 10.1007/s007050050246 . PMID 9672598 .
External links[ edit ]
- Häusler, T. (2006) “Viruses vs. Superbugs”, Macmillan
- Animation of bacteriophage targeting E. coli bacteria
- Phage.org general information on bacteriophages
- bacteriophages illustrations and genomics
- Bacteriophages get a foothold on their prey
- NPR Science Friday podcast, “Using ‘Phage’ Viruses to Help Fight Infection”, April 2008
- Animation by Hybrid Animation Medical for a T4 Bacteriophage targeting E. coli bacteria.
- Bacteriophages: What are they. Presentation by Professor Graham Hatfull, University of Pittsburgh on YouTube
- CS1 French-language sources (fr)
- Webarchive template wayback links
- Use dmy dates from July 2012
- This page was last edited on 31 October 2018, at 13:50 (UTC).
- Text is available under the Creative Commons Attribution-ShareAlike License ;
- About Wikipedia
- Contact Wikipedia
- Cookie statement
- Mobile view