Article notes - Phage whisperer Flashcards
Why aren’t pharmaceutical companies interested in doing research on new antibiotics?
Pharmaceutical companies are not interested in doing research on new antibiotics because the problem with AMR is causing a major threat to global health and developing a new antibiotic cost a lot and if this antibiotic has a short shelf-life because of AMR, then pharmaceutical companies see no purpose
What personal interest does the author have in this issue?
The personal interest that the author has with the issue is her husband had contracted a superbug called Acinetobacterbaumannii, in which every antibiotic doctors were trying
was not working as the superbug was resistant to it. Doctors then tried to do a drain of his abscesses, but as it was working it ended up falling into his bloodstream causing septic shock and having him in and out of a coma. This is when the author did their research and
found an old cure of phages, called phage therapy
When and where was bacteriophage therapy first tested?
The first bacteriophage therapy was in 1919 where self-taught microbiologist
Felix d’Herelle came up with the therapy, he was able to successfully treat sick
children with dysentery during an outbreak in Paris
When did interest in bacteriophages wane in the West? Why?
Interest in bacteriophages decreased in the West due to the first antibiotic, penicillin, being released on the market in 1942 and thus phage therapy fell out
Where did bacteriophage therapy continue to be used and optimized?
Bacteriophage therapy is continued in some parts of Eastern Europe and Republic
of Georgia because they have a short supply of antibiotics
Is it currently approved by the FDA in the U.S.?
No, bacteriophage therapy is not currently approved by the FDA in the U.S as it
requires to show that it is safe and efficacious, but that has not been conducted.
Why is it better to use a lytic phage than a lysogenic phage for phage therapy?
It is better to use a lytic phage than a lysogenic phage because lysogenic phages often carry AMR genes or toxin genes that can cause the bacterial cell to be impervious to attacks from other phages, while lytic phages kill the bacteria via lysis
How is phage therapy different from antibiotic therapy? Advantages? Disadvantages?
Phage therapy is different from antibiotic therapy as the phages are very specific, so they bind to the bacteria that only carries the receptors that are a match, and it then latches onto the bacterial cell and drill into it in order to inject their genetic material into the bacterium. Lytic phages change the bacterium into a phage manufacturing and makes copies of itself and then when the signal is given the phages burst out of the bacterium, this is lysis. They repeat this process until there is no bacteria left and then they are filtered out by the liver and spleen. The advantages of this are that it does not cause AMR
and it is specific so it won’t harm any other bacteria in the microbiome, but because it is so specific a phage hunt is necessary to find which phage would match the bacteria. Antibiotic therapy attacks all bacteria in the microbiome, as they are broad-spectrum antibiotics, thus making it easier to become AMR
What did it take for Dr. Strathdee’s initial idea to become a reality?
To make Dr. Strathdee’s initial idea to become a reality, it took a whole global
community, from researchers who have published papers on A. baumannii, to then
having researchers from different international phage communities as well as
biotech companies. All these different people coming together and finding more
connections to help save Dr. Patterson’s life and make Dr. Strathdee’s idea a
reality
How were the phages introduced into Dr. Patterson’s body?
The phages were introduced via injections and infusions, one billion viral particles per dose. The Navy phages were infused into his bloodstream, while the Texas phage cocktail was injected into Dr. Patterson’s abdominal catheters
How soon after the therapy did he wake up from his coma?
Dr. Patterson woke up from his coma about a few days later after having the Navy
phages infused into his bloodstream
How did his recovery progress?
Dr. Patterson’s recovery progress was long but successful, but his bacterial isolate did become resistant to the initial phage cocktail, but this is when the Navy team generated a second phage cocktail within days and with two phages which were synergistic with an antibiotic it caused selective pressure making the A.
baumannii to become susceptible to an antibiotic which had previously been
resistant to
In your own words, describe the case of Isabelle Carnell Holdaway
Isabelle Carnell Holdaway was a teenager living in the UK who had undergone
double lung transplant due to cystic fibrosis, but she got infected with a superbug
called Mycobacterium abscessus, and it was attacking her new lungs. Isabelle’s mother investigated phage therapy and asked the doctor to pursue it. Professor
Graham Hatfull was approached and started to undergo a phage hunt to fins any phages that could kill Isabelle’s phage via lytic. They only found 3 phages, one
capable of lytic and two who were temperate phages. Although temperate phages
are not ideal as they carry toxins or AMR genes, but with no option left, Professor
Graham and his team did recombineering of the temperate phages and helped clip out the repressor gene, forcing them to become lytic. This was the first genetically
modified phage cocktail
How was her treatment different than that of Dr. Patterson?
Isabelle’s treatment was different than Dr. Patterson as Isabelle had genetically
modified phage cocktails, while Dr. Patterson did not. Isabelle’s phages had to be
modified for them to become lytic as they had previously been temperate.
