Bacteriophage – Flashcards

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  • Viruses that infect bacteria and require bacterial host for replication

    Obligate intracellular parasites that consist of a protein coat surrounding a central nucleic acid core

    Considerable diversity exists among bacterial viruses in both physical structure and nucleic acid content




Bacteriophages: The Basics

Tend to have large genomes and complex structure

Most phage are dsDNA viruses but some are ssDNA, ssRNA, or dsRNA

Phage head (protein) contains nucleic acid

Viral ligand that interacts with bacterial receptor located on tail fibers

Sheath (hollow) contracts in some phage during binding to bacterial cell

Most infect by drilling a hole through peptidoglycan and injecting DNA directly into bacterial cell while the rest of the virus stays extracellular





Bacteriophage: Infection

-Adsorption of the phage to the bacterial cells
-Sheath contraction
-Nucleic acid injection




Phage Multiplication: Lytic 

-Lytic(replication culminates in lysing and thus killing bacterium)
-Phage takes over host biosynthetic machinery
-Phage mRNAs and proteins produced, sometimes degrading host chromosome
-New phage particles are assembled inside bacterium
-Bacterium lyses due to accumulation of phage lysis protein
-Intracellular phage released; up to 1000 phage/bacterium possible




Phage Multiplication: Lysogenic

-Lysogenic/temperate (quiescent state in the bacterium such that host is unharmed)
-Phage chromosome circularizes
-Phage-encoded enzyme performs recombination between particular site on circularized phage and particular site on host chromosome– integration of the phage DNA occurs– cell now referred to as lysogen

-Phage genome is repressed by phage-encoded repressor protein





-The transfer of viral or bacterial, or both, DNA from one cell to another via bacteriophage




Mechanisms of Transduction

Bacterial gene transfer via a virus particle:
-During assembly stage of lytic replication, DNA fragments from host genome are packaged instead of phage DNA  (GENERALIZED)
-During excision of prophage, fragment of chromosomal DNA can be excised with phage DNA (SPECIALIZED)

Lysogenic conversion: Prophage genes (inserted into chromosome) can increase the survival fitness of the host cell in particular situations: 
-Phage repressor and super-infection exclusion provide immunity to the host against lytic infection
-Can convert non-pathogenic bacterial strains into pathogenic ones (encode toxins, for example)




Bacteriophages as Antibiotics?

Harness the potential of phage to quickly lyse/kill bacterial host

Once it infects its target, it quickly (about 30 min) generates 100s of copies of itself that search out additional microbes to kill

Because phages are ‘living’ organisms (unlike antibiotics), they can evolve as the bacteria evolve; so as bacteria evolve to resist phage, the phage evolves too

Infect only bacteria so they are harmless to mammalian cells and to non-target bacteria (unlike antibiotics), which leaves beneficial gut flora intact





Problems with Phage Therapy

Because one phage typically infects only one type of bacterium, you must know what a person is infected with prior to treatment and usually need to use a cocktail of phages

Most phages elicit a strong antibody response such that only one treatment will be possible

There is potential to release large quantities of endotoxin from lysed bacterial cells

Most pharmaceutical companies are not interested in investing in clinical trials (very expensive) because they cannot patent the rights to phage therapy (the concept is almost 100 years old)


**However, due to emergence of many antibiotic-resistant bugs in recent years, some human phage therapies are becoming available

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