Bacteriophages

1. Bacteriophages Scientistmel.com Twitter.com/scientistmel Patreon.com/scientistmel 8-18-2018 10 am CST

2. Bacteriophages • What are they? • What are the types? • What do they do? • How are they useful to us?

3. Bacteriophages • Viruses that infect bacteria • Contain DNA or RNA (4 genes to hundreds) • Most abundant “organism” • Drivers of bacterial evolution

4. Bacteriophages

5. Bacteriophages • Virus infects bacteria • Releases genetic code into bacteria

6. Bacteriophages • Life Cycles • Lytic and Lysogenic

7. Bacteriophages • Khan academy hasa simplified article discussing bacteriophages if you are interested…I reference them • The stages of the lytic cycle are: • Attachment: Proteins in the "tail" of the phage bind to a specific receptor (in this case, a sugar transporter) on the surface of the bacterial cell. • Entry: The phage injects its double-stranded DNA genome into the cytoplasm of the bacterium. • DNA copying and protein synthesis: Phage DNA is copied, and phage genes are expressed to make proteins, such as capsid proteins. • Assembly of new phage: Capsids assemble from the capsid proteins and are stuffed with DNA to make lots of new phage particles. • Lysis: Late in the lytic cycle, the phage expresses genes for proteins that poke holes in the plasma membrane and cell wall. The holes let water flow in, making the cell expand and burst like an overfilled water balloon. • Cell bursting, or lysis, releases hundreds of new phages, which can find and infect other host cells nearby. In this way, a few cycles of lytic infection can let the phage spread like wildfire through a bacterial population.

8. Bacteriophages

9. Bacteriophages • The lysogenic cycle allows a phage to reproduce without killing its host. Some phages can only use the lytic cycle, but the phage we are following, lambda (\lambdaλlambda), can switch between the two cycles. [Do all phages use one of these two strategies?] • ^{7,8}start superscript, 7, comma, 8, end superscript • In the lysogenic cycle, the first two steps (attachment and DNA injection) occur just as they do for the lytic cycle. However, once the phage DNA is inside the cell, it is not immediately copied or expressed to make proteins. Instead, it recombines with a particular region of the bacterial chromosome. This causes the phage DNA to be integrated into the chromosome. [Is this true of all phages?]

10. Bacteriophages

11. Bacteriophages • Most phages are either purely lytic (sometimes called virulent phages) or capable of switching between the lytic and lysogenic cycles (sometimes called temperate phages). • However, when it comes to virology, there is an exception to almost every rule, and this is true for phage lifecycles. Filamentous (long, rod-shaped) phages are secreted from the cell in a process that does not lyse or kill the cell (even though the cell is actively producing new phage particles. This is a "lytic-like" lifecycle that does not actually involve lysis. • Not all phages integrate their DNA into the genome of their host during the lysogenic cycle. Some instead keep their genome in the cell as a separate, circular piece of DNA. • This is still considered a lysogenic cycle because the phage does not drive production of new virus particles or kill the cell. Instead, it remains "silent" and is passively copied along with the cell's DNA.

12. Bacteriophages • How does a phage "decide" whether to enter the lytic or lysogenic cycle when it infects a bacterium? One important factor is the number of phages infecting the cell at once^99start superscript, 9, end superscript. Larger numbers of co-infecting phages make it more likely that the infection will use the lysogenic cycle. This strategy may help prevent the phages from wiping out their bacterial hosts (by toning down the attack if the phage-to-host ratio gets too high)^{10}10start superscript, 10, end superscript. [Hide explanation] • When there are multiple phages infecting a single bacterium, that suggests (statistically speaking) that the phages may be in danger of wiping out their bacterial hosts^33start superscript, 3, end superscript. • Phages that flip to the lysogenic mode in response to a high multiplicity of infection may be less likely to run out of hosts and "die out" as a population (because they can strategically stop killing hosts once their own numbers get too high). Notably, once a cell has a prophage in its genome, it is immune to being infected by another phage of the same typeThus, the genetically encoded tendency to flip to lysogeny at at high multiplicity might have been favored by natural selection (explaining why phages have it today). • What triggers a prophage to pop back out of the chromosome and enter the lytic cycle? At least in the laboratory, DNA-damaging agents (like UV radiation and chemicals) will trigger most prophages in a population to re-activate. However, a small fraction of the prophages in a population spontaneously "go lytic" even without these external cues

13. Bacteriophages • Cholera • Diptheria • Hemorrhagicdiarrhea • Botulism • Scarlet Fever

14. Bacteriophages • Genetic code is universal. So these bacteria infecting viruses utilize the ribosomes and the easily modified genetic code of bacteria (no nucleus) to altered the bacteria to produce these toxins. The bacteria reads the code injected by the virus and follows directions…generating proteins that make us crazy ill and oftentimes it is lethal. • But there is something interesting about the fact these viruses can genetically modify bacteria…is this a solution to the “antibiotic resistant bacteria”? Letet’s have a look at the history of using bacteriophages to combat harmful bacteria

15. Bacteriophages • Some controversy over discovery • Possibly first discovered in 1896/189 • First discovered in 1915 • Discovered to be lethal in 1917

16. Bacteriophages • Ernest Hankin, a British bacteriologist, reported in 1896 antibacterial activity against Vibrio cholerae. He observed this in the Ganges and Jumna rivers in India. It was his thought thAT an unidentified substance was responsible for this as well as limiting the spread of cholera epidemics. Two years later, the Russian bacteriologist Gamaleya observed a similar phenomenon while working with Bacillus subtilis. It wasn’t until Frederick Twort (an English medically trained bacteriologist) who observed the same phenomenon as the other 2 investigators…but suggested it could be a virus. The first fundamental textbook discovery these bacteriophages and later to found to be lethal to bacteria in 1917 is by Felix d’Herelle…a microbiologist at the Pastuer Institute in Paris.

17. Bacteriophages • Antibiotic resistance among pathogenic bacteria is becoming a serious issue as infections are harder to treat. The use bacteriophages to kill specific bacterial pathogens is gaining more ground as a potential treatment for infections. Bacteriophage therapy was widely used in the 1930s and 1940s. It is still used in portions of Eastern Europe and the former Soviet Union. In the west, a lot of the research and use of bacteriophages to treat bacterial pathogen infections was abandoned once antibiotics hit the scene. Now, medical science is moving to use more bacteriophages in treatment of these infections as the bacteriophages do not harm human cells. Now with emergence of immunotherapies for treatments of more debilitating illness like cancers, incorporating well established research of bacteriophages into medical treatment of bacterial infections, this is an emerging answer to the rampant issue of antibiotic resistant bacteria.

18. Bacteriophages • Viruses that infect bacteria • Contain DNA or RNA (4 genes to hundreds) • Most abundant “organism” • Drivers of bacterial evolution

19. Bacteriophages • What are they? • What are the types? • What do they do? • How are they useful to us?

20. Bacteriophages • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3916379/ • https://www.ncbi.nlm.nih.gov/pubmed/11730156 • https://www.tandfonline.com/doi/abs/10.3109/07853890108995959 • http://www.sci.sdsu.edu/~smaloy/MicrobialGenetics/topics/phage/phage-virulence.html • https://mbio.asm.org/content/8/5/e01579-17 • https://academic.oup.com/femsle/article/363/7/fnw047/2197796 • https://www.researchgate.net/figure/Families-of-bacteriophages-grouped-according-to-their-most-common-nucleic-acid_fig2_249644135 • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351/ • https://www.khanacademy.org/science/biology/biology-of-viruses/virus-biology/a/bacteriophages • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109452/

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23. Bacteriophages Scientistmel.com Twitter.com/scientistmel Patreon.com/scientistmel 8-18-2018 10 am CST