Bacteriophage

Source: Wikipedia, the free encyclopedia.
(Redirected from
Bacteriophages
)
"Phage" redirects here. For other uses, see Phage (disambiguation).

Structural model at atomic resolution of bacteriophage T4[1]
The structure of a typical myovirus bacteriophage
Anatomy and infection cycle of bacteriophage T4.

A bacteriophage (

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

marine bacteria may be infected by bacteriophages.[6]

Bacteriophages were used from the 1920s as an alternative to

multi-drug-resistant strains of many bacteria (see phage therapy).[9][10][11][12]

Bacteriophages are known to interact with the immune system both indirectly via bacterial expression of phage-encoded proteins and directly by influencing innate immunity and bacterial clearance.[13] Phage–host interactions are becoming increasingly important areas of research.[14]

Classification

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.

Bacteriophage P22, a member of the Podoviridae by morphology due to its short, non-contractile tail
Bacteriophage T2, a member of the Myoviridae due to its contractile tail
ICTV classification of prokaryotic (bacterial and archaeal) viruses[2]
Order Family Morphology Nucleic acid Examples
Belfryvirales
 		Turriviridae Enveloped, isometric Linear dsDNA
Caudovirales Ackermannviridae Nonenveloped, contractile tail Linear dsDNA
Autographiviridae Nonenveloped, noncontractile tail (short) Linear dsDNA
Chaseviridae Linear dsDNA
Demerecviridae Linear dsDNA
Drexlerviridae Linear dsDNA
Guenliviridae Linear dsDNA
Herelleviridae Nonenveloped, contractile tail Linear dsDNA
Myoviridae Nonenveloped, contractile tail Linear dsDNA
Mu, P1, P2
Siphoviridae Nonenveloped, noncontractile tail (long) Linear dsDNA
N15
Podoviridae Nonenveloped, noncontractile tail (short) Linear dsDNA
P22
Rountreeviridae Linear dsDNA
Salasmaviridae Linear dsDNA
Schitoviridae Linear dsDNA
Zobellviridae Linear dsDNA
Halopanivirales
Sphaerolipoviridae
 Enveloped, isometric Linear dsDNA
Simuloviridae
 Enveloped, isometric Linear dsDNA
Matshushitaviridae
 Enveloped, isometric Linear dsDNA
Haloruvirales
 		Pleolipoviridae Enveloped, pleomorphic Circular ssDNA, circular dsDNA, or linear dsDNA
Kalamavirales
Tectiviridae
 Nonenveloped, isometric Linear dsDNA
Ligamenvirales Lipothrixviridae Enveloped, rod-shaped Linear dsDNA
Acidianus filamentous virus 1
Rudiviridae Nonenveloped, rod-shaped Linear dsDNA
Sulfolobus islandicus rod-shaped virus 1
Mindivirales
Cystoviridae
 Enveloped, spherical Linear dsRNA Φ6
Norzivirales Atkinsviridae Nonenveloped, isometric Linear ssRNA
Duinviridae Nonenveloped, isometric Linear ssRNA
Fiersviridae Nonenveloped, isometric Linear ssRNA
Qβ
Solspiviridae Nonenveloped, isometric Linear ssRNA
Petitvirales
 		Microviridae Nonenveloped, isometric Circular ssDNA ΦX174
Primavirales
 		Tristromaviridae Enveloped, rod-shaped Linear dsDNA
Timlovirales Blumeviridae Nonenveloped, isometric Linear ssRNA
Steitzviridae Nonenveloped, isometric Linear ssRNA
Tubulavirales
Inoviridae
 Nonenveloped, filamentous Circular ssDNA M13
Paulinoviridae Nonenveloped, filamentous Circular ssDNA
Plectroviridae Nonenveloped, filamentous Circular ssDNA
Vinavirales
Corticoviridae
 Nonenveloped, isometric Circular dsDNA
PM2
Durnavirales
Picobirnaviridae
 (proposal)		 Nonenveloped, isometric Linear dsRNA
Unassigned Ampullaviridae Enveloped, bottle-shaped Linear dsDNA
Autolykiviridae Nonenveloped, isometric Linear dsDNA
Bicaudaviridae Nonenveloped, lemon-shaped Circular dsDNA
Clavaviridae Nonenveloped, rod-shaped Circular dsDNA
Finnlakeviridae Nonenveloped, isometric Circular ssDNA
FLiP[15]
Fuselloviridae Nonenveloped, lemon-shaped Circular dsDNA Alphafusellovirus
Globuloviridae Enveloped, isometric Linear dsDNA
Guttaviridae Nonenveloped, ovoid Circular dsDNA
Halspiviridae Nonenveloped, lemon-shaped Linear dsDNA
Plasmaviridae Enveloped, pleomorphic Circular dsDNA
Portogloboviridae Enveloped, isometric Circular dsDNA
Thaspiviridae Nonenveloped, lemon-shaped Linear dsDNA
Spiraviridae Nonenveloped, rod-shaped Circular ssDNA

It has been suggested that members of

Picobirnaviridae infect bacteria, but not mammals.[16]

There are also many unassigned genera of the class Leviviricetes: Chimpavirus, Hohglivirus, Mahrahvirus, Meihzavirus, Nicedsevirus, Sculuvirus, Skrubnovirus, Tetipavirus and Winunavirus containing linear ssRNA genomes[17] and the unassigned genus Lilyvirus of the order Caudovirales containing a linear dsDNA genome.

History

Félix d'Herelle
conducted the first clinical application of a bacteriophage

In 1896, Ernest Hanbury Hankin reported that something in the waters of the Ganges and Yamuna rivers in India had a marked antibacterial action against cholera and it could pass through a very fine porcelain filter.[18] 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:

  1. a stage in the life cycle of the bacteria
  2. an enzyme produced by the bacteria themselves, or
  3. a virus that grew on and destroyed the bacteria[19]

Twort's research was interrupted by the onset of World War I, as well as a shortage of funding and the discoveries of antibiotics.

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."[20] D'Hérelle called the virus a bacteriophage, a 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.[21] It was d'Hérelle who conducted much research into bacteriophages and introduced the concept of phage therapy.[22] In 1919, in Paris, France, d'Hérelle conducted the first clinical application of a bacteriophage, with the first reported use in the United States being in 1922.[23]

Nobel prizes awarded for phage research

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.[24] Specifically the work of Hershey, as contributor to the Hershey–Chase experiment in 1952, provided convincing evidence that DNA, not protein, was the genetic material of life. Delbrück and Luria carried out the Luria–Delbrück experiment which demonstrated statistically that mutations in bacteria occur randomly and thus follow Darwinian rather than Lamarckian principles.

Uses

Phage therapy

Main article: Phage therapy
George Eliava pioneered the use of phages in treating bacterial infections

Phages were discovered to be antibacterial agents and were used in the former

Giorgi Eliava with help from the co-discoverer of bacteriophages, Félix d'Hérelle) during the 1920s and 1930s for treating bacterial infections. They had widespread use, including treatment of soldiers in the Red Army.[25]
However, they were abandoned for general use in the West for several reasons:

The use of phages has continued since the end of the

biofilms involved in pneumonia and cystic fibrosis and to shelter the bacteria from drugs meant to eradicate disease, thus promoting persistent infection.[30]

Meanwhile, bacteriophage researchers have been developing engineered viruses to overcome antibiotic resistance, and engineering the phage genes responsible for coding enzymes that degrade the biofilm matrix, phage structural proteins, and the enzymes responsible for lysis of the bacterial cell wall.[5][6][7] 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.[31]

Therapeutic efficacy of a phage cocktail was evaluated in a mice model with nasal infection of multidrug-resistant (MDR)

A. baumannii. Mice treated with the phage cocktail showed a 2.3-fold higher survival rate compared to those untreated at seven days post-infection.[32] In 2017, a patient with a pancreas compromised by MDR A. baumannii was put on several antibiotics; despite this, the patient's health continued to deteriorate during a four-month period. 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. baumannii. Once on this therapy the patient's downward clinical trajectory reversed, and returned to health.[33]

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."[34] This includes rivers traditionally thought to have healing powers, including India's Ganges River.[35]

Other

Food industry

Phages have increasingly been used to safen food products and to forestall

Micreos) using bacteriophages on cheese to kill Listeria monocytogenes bacteria, in order to give them generally recognized as safe (GRAS) status.[37] In July 2007, the same bacteriophage were approved for use on all food products.[38] In 2011 USDA confirmed that LISTEX is a clean label processing aid and is included in USDA.[39] 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.[40]

Water indicators

Bacteriophages, including those specific to Escherichia coli, have been employed as indicators of fecal contamination in water sources. Due to their shared structural and biological characteristics, coliphages can serve as proxies for viral fecal contamination and the presence of pathogenic viruses such as rotavirus, norovirus, and HAV. Research conducted on wastewater treatment systems has revealed significant disparities in the behavior of coliphages compared to fecal coliforms, demonstrating a distinct correlation with the recovery of pathogenic viruses at the treatment's conclusion. Establishing a secure discharge threshold, studies have determined that discharges below 3000 PFU/100 mL are considered safe in terms of limiting the release of pathogenic viruses. [41]

Diagnostics

In 2011, the FDA cleared the first bacteriophage-based product for in vitro diagnostic use.[42] 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 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.[43]

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.[44] Developments are continuing among research groups in the U.S. 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[29] show success in veterinary treatment of pet dogs with otitis.

Bacterium sensing and identification

The sensing of phage-triggered ion cascades (SEPTIC) bacterium sensing and identification method uses the ion emission and its dynamics during phage infection and offers high specificity and speed for detection.[45]

Phage display

Phage display is a different use of phages involving a library of phages with a variable peptide linked to a surface protein. 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.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.[46]

Antimicrobial drug discovery

Phage proteins often have antimicrobial activity and may serve as leads for

endotoxin) and lysis of bacteria.[48]

Basic research

Bacteriophages are important

model organisms for studying principles of evolution and ecology.[49]

Detriments

Dairy industry

Bacteriophages present in the environment can cause cheese to not ferment. In order to avoid this, mixed-strain starter cultures and culture rotation regimes can be used.

phage resistance. This has especially focused on plasmid and recombinant chromosomal modifications.[51][36]

Some research has focused on the potential of bacteriophages as antimicrobial against foodborne pathogens and biofilm formation within the dairy industry. As the spread of antibiotic resistance is a main concern within the dairy industry, phages can serve as a promising alternative.[52]

Replication

Diagram of the DNA injection process

The life cycle of bacteriophages tends to be either a lytic cycle or a lysogenic cycle. In addition, some phages display pseudolysogenic behaviors.[13]

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.[13] 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 the temperate phage going dormant and usually is temporary.[53]

In contrast, the

phage lambda of E. coli.[54]

Sometimes prophages may provide benefits to the host bacterium while they are dormant by adding new functions to the bacterial

lysogenic conversion. 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.[55][56] Strategies to combat certain bacterial infections by targeting these toxin-encoding prophages have been proposed.[57]

Attachment and penetration

electron micrograph
of bacteriophages attached to a bacterial cell, the viruses are the size and shape of coliphage T1

Bacterial cells are protected by a cell wall of

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. Polysaccharide-degrading enzymes are virion-associated proteins that enzymatically degrade the capsular outer layer of their hosts at the initial step of a tightly programmed phage infection process.[citation needed
] Host growth conditions also influence the ability of the phage to attach and invade them.[59] As phage virions do not move independently, they must rely on random encounters with the correct receptors when in solution, such as blood, lymphatic circulation, irrigation, soil water, etc.[citation needed]

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,[6] injecting genetic material through the bacterial membrane.[60]
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

Within minutes, bacterial

University of Ghent, Belgium) was the first to establish the complete nucleotide sequence of a gene and in 1976, of the viral genome of bacteriophage MS2.[61] Some dsDNA bacteriophages encode ribosomal proteins, which are thought to modulate protein translation during phage infection.[62]

Virion assembly

In the case of the

T4 phage, the construction of new virus particles involves the assistance of helper proteins that act catalytically during phage morphogenesis.[63] 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. During assembly of the phage T4 virion, the morphogenetic proteins encoded by the phage genes interact with each other in a characteristic sequence. Maintaining an appropriate balance in the amounts of each of these proteins produced during viral infection appears to be critical for normal phage T4 morphogenesis.[64] The DNA is packed efficiently within the heads.[65]
The whole process takes about 15 minutes.

Release of virions

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

lysogenic cycle do not kill the host and instead become long-term residents as prophages.[66]

Communication

Research in 2017 revealed that the bacteriophage Φ3T makes a short viral protein that signals other bacteriophages to lie dormant instead of killing the host bacterium. Arbitrium is the name given to this protein by the researchers who discovered it.[67][68]

Genome structure

Given the millions of different phages in the environment, phage genomes come in a variety of forms and sizes. RNA phages such as

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).[72] Evolutionary mechanisms shaping the genomes of bacterial viruses vary between different families and depend upon the type of the nucleic acid, characteristics of the virion structure, as well as the mode of the viral life cycle.[73]

Some marine roseobacter phages contain deoxyuridine (dU) instead of deoxythymidine (dT) in their genomic DNA. There is some evidence that this unusual component is a mechanism to evade bacterial defense mechanisms such as restriction endonucleases and CRISPR/Cas systems which evolved to recognize and cleave sequences within invading phages, thereby inactivating them. Other phages have long been known to use unusual nucleotides. In 1963, Takahashi and Marmur identified a Bacillus phage that has dU substituting dT in its genome,[74] and in 1977, Kirnos et al. identified a cyanophage containing 2-aminoadenine (Z) instead of adenine (A).[75]

Systems biology

The field of systems biology investigates the complex networks of interactions within an organism, usually using computational tools and modeling.[76] For example, a phage genome that enters into a bacterial host cell may express hundreds of phage proteins which will affect the expression of numerous host genes or the host's metabolism. All of these complex interactions can be described and simulated in computer models.[76]

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.[77]

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 dozens of interactions. 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.[78]

Host resistance

Bacteriophages are a major threat to bacteria and prokaryotes have evolved numerous mechanisms to block infection or to block the replication of bacteriophages within host cells. The CRISPR system is one such mechanism as are retrons and the anti-toxin system encoded by them.[79] The Thoeris defense system is known to deploy a unique strategy for bacterial antiphage resistance via NAD+ degradation.[80]

Bacteriophage–host symbiosis

Temperate phages are bacteriophages that integrate their genetic material into the host as extrachromosomal episomes or as a prophage during a lysogenic cycle.[81][82][83] Some temperate phages can confer fitness advantages to their host in numerous ways, including giving antibiotic resistance through the transfer or introduction of antibiotic resistance genes (ARGs),[82][84] protecting hosts from phagocytosis,[85][86] protecting hosts from secondary infection through superinfection exclusion,[87][88][89] enhancing host pathogenicity,[81][90] or enhancing bacterial metabolism or growth.[91][92][93][94] Bacteriophage–host symbiosis may benefit bacteria by providing selective advantages while passively replicating the phage genome.[95]

In the environment

Main article:
Marine bacteriophage

Metagenomics has allowed the in-water detection of bacteriophages that was not possible previously.[96]

Also, bacteriophages have 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.[97] Non-polluted water may contain approximately 2×108 bacteriophages per ml.[98]

Bacteriophages are thought to contribute extensively to

multidrug resistance.[100]

Recent findings have mapped the complex and intertwined arsenal of anti-phage defense tools in environmental bacteria.[101]

In humans

Although phages do not infect humans, there are countless phage particles in the human body, given our extensive microbiome. Our phage population has been called the human phageome, including the "healthy gut phageome" (HGP) and the "diseased human phageome" (DHP).[102] The active phageome of a healthy human (i.e., actively replicating as opposed to nonreplicating, integrated prophage) has been estimated to comprise dozens to thousands of different viruses.[103] There is evidence that bacteriophages and bacteria interact in the human gut microbiome both antagonistically and beneficially.[104]

Preliminary studies have indicated that common bacteriophages are found in 62% of healthy individuals on average, while their prevalence was reduced by 42% and 54% on average in patients with ulcerative colitis (UC) and Crohn's disease (CD).[102] Abundance of phages may also decline in the elderly.[104]

The most common phages in the human intestine, found worldwide, are

primates besides humans.[104]

Commonly studied bacteriophage

Among the countless phage, only a few have been studied in detail, including some historically important phage that were discovered in the early days of microbial genetics. These, especially the T-phage, helped to discover important principles of gene structure and function.

Bacteriophage databases and resources

See also

References

  1. S2CID 238939621
    .
  2. ^
    ISBN 978-1-904455-14-1
    .
  3. ^ LaFee S, Buschman H (25 April 2017). "Novel Phage Therapy Saves Patient with Multidrug-Resistant Bacterial Infection". UC Health – UC San Diego. Retrieved 13 May 2018.
  4. S2CID 4370363
    .
  5. ^
    PMID 10704475
    .
  6. ^
    ISBN 0-697-01372-3
    .
  7. ^
    OCLC 224991186
    . – Documentary about the history of phage medicine in Russia and the West
  8. JSTOR 26016042
    .
  9. S2CID 73439131
    .
  10. PMID 30651225
    .
  11. PMID 32899720
    .
  12. PMID 22833738
    .
  13. ^
    PMID 34014761
    .
  14. PMID 31216787
    .
  15. PMID 28716906
    .
  16. PMID 29346073
    .
  17. doi:10.13140/RG.2.2.25363.40481
    .
  18. ^ Hankin EH (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: 511–23.
  19. doi:10.1016/S0140-6736(01)20383-3
    .
  20. ^ d'Hérelles F (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 11 May 2011. Retrieved 5 September 2010.
  21. ^ d'Hérelles F (1949). "The bacteriophage" (PDF). Science News. 14: 44–59. Retrieved 5 September 2010.
  22. PMID 23231482
    .
  23. PMID 34172535
    .
  24. ^ "The Nobel Prize in Physiology or Medicine 1969". Nobel Foundation. Retrieved 28 July 2007.
  25. PMID 30312428
    .
  26. S2CID 31626252
    .
  27. Наука и жизнь
     [Nauka I Zhizn (Science and life)] (in Russian) (6): 26–33.
  28. ^
    PMID 19661847
    .
  29. ^
    PMID 19673983
    .
  30. PMID 30923196
    .
  31. PMID 22609555. Archived
    (PDF) from the original on 2 February 2023.
  32. PMID 29755420
    .
  33. PMID 28807909
    .
  34. ISBN 978-1-4614-0250-3
  35. PMID 19275495
    .
  36. ^
    S2CID 58620015
    .
  37. ^ U.S. FDA/CFSAN: Agency Response Letter, GRAS Notice No. 000198
  38. ^ (U.S. FDA/CFSAN: Agency Response Letter, GRAS Notice No. 000218)
  39. ^ "FSIS Directive 7120: Safe and Suitable Ingredients Used in the Production of Meat, Poultry, and Egg Products" (PDF). Food Safety and Inspection Service. Washington, DC: United States Department of Agriculture. Archived from the original (PDF) on 18 October 2011.
  40. PMID 37869651
    .
  41. ^ Chacón L, Barrantes K, Santamaría-Ulloa C, Solano MReyes L, Taylor LValiente C, Symonds EM, Achí R. 2020. A Somatic Coliphage Threshold Approach To Improve the Management of Activated Sludge Wastewater Treatment Plant Effluents in Resource-Limited Regions. Appl Environ Microbiol 86:e00616-20. https://doi.org/10.1128/AEM.00616-20/
  42. ^ "FDA 510(k) Premarket Notification". U.S. Food and Drug Administration.
  43. PMID 32591380. Archived from the original
    on 5 April 2024.
  44. ^ Vaisman D (25 May 2007). "Studying anthrax in a Soviet-era lab – with Western funding". The New York Times.
  45. doi:10.4024/1050501.jbpc.05.01. Archived from the original
    (PDF) on 26 September 2018. Retrieved 19 December 2016.
  46. PMID 11848876
    .
  47. S2CID 9905115
    .
  48. ^ "Technological background Phage-ligand technology". bioMérieux.
  49. PMID 24616839
    .
  50. PMID 23882262
    .
  51. S2CID 7217985
    .
  52. PMID 29117107
    .
  53. PMID 31623057
    .
  54. ISBN 978-0-07-893649-4
    .
  55. PMID 19007916
    .
  56. S2CID 6907842
    .
  57. PMID 23248780
    .
  58. PMID 25666799
    .
  59. PMID 9356254
    .
  60. PMID 31767752
    .
  61. S2CID 4289674
    .
  62. PMID 30765709
    .
  63. PMID 4878023
    .
  64. PMID 4907266
    .
  65. PMID 18487310
    .
  66. S2CID 252542284
    .
  67. doi:10.1038/nature.2017.21313
    .
  68. PMID 28099413
    .
  69. PMID 22297527
    .
  70. PMID 32051592
    .
  71. PMID 22748812
    .
  72. PMID 18178732
    .
  73. PMID 22126996
    .
  74. S2CID 4166988
    .
  75. S2CID 4177449
    .
  76. ^
    OCLC 288986435
    .
  77. PMID 26750429
    .
  78. PMID 24049175
    .
  79. S2CID 250643138
    .
  80. PMID 32499527
    .
  81. ^
    PMID 34071422
    .
  82. ^
    PMID 33347602
    .
  83. PMID 34255542
    .
  84. PMID 19858262
    .
  85. S2CID 203580138
    .
  86. S2CID 204243652
    .
  87. PMID 24659988
    .
  88. S2CID 7084706
    .
  89. OCLC 679550931
    .
  90. PMID 15353570
    .
  91. S2CID 4156346
    .
  92. PMID 25501487
    .
  93. PMID 25706310
    .
  94. S2CID 3565635
    .
  95. PMID 36204422
    .
  96. PMID 12384570
    .
  97. doi:10.1111/j.1747-6593.1988.tb01352.x
    .
  98. S2CID 4271861
    .
  99. PMID 28096488
    .
  100. PMID 27890586
    .
  101. PMID 38459056
    .
  102. ^
    PMID 27573828
    .
  103. PMID 21880779
    .
  104. ^
    PMID 34255542
    .
  105. PMID 13978804
    .
  106. PMID 12626685
    .
  107. S2CID 39369249
    .
  108. PMID 37904614
    .

Bibliography

External links

Wikimedia Commons has media related to Bacteriophages.
Wikiquote has quotations related to Bacteriophage.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Bacteriophage&oldid=1217513200"