Phage Therapy and Bacterial Resistance

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Questions and Answers

What is defined as high persistence in phage therapy?

Maintaining a Rφ below 0.03 for at least 3 hours

Maintaining a Rφ below 0.03 for at least 4 hours

Maintaining a Rφ above 0.03 for at least 4 hours (correct)

Maintaining a Rφ above 0.03 for at least 3 hours

Which assumption about lytic phages during phage therapy is considered pessimistic?

A latent period of less than 30 minutes

A burst size of at least 5

A burst size of at least 15

A latent period of less than 45 minutes (correct)

What is a key difference between phage therapy and antibiotic therapy?

Phage therapy requires precise definitions of persistence, unlike antibiotic therapy.

Phage therapy is restricted to viral infections, while antibiotic therapy targets bacteria.

Phage therapy is considered biomedicine, while antibiotic therapy is classified as chemo-medicine. (correct)

Phage therapy is more effective against all types of infections compared to antibiotics.

What is the primary challenge for obtaining FDA approval for phage therapy?

The variability in the individual characteristics of phages Signup and view all the answers

What vessel has been used as an analogy for FDA approval considerations in biomedicine?

Leeches Signup and view all the answers

Which of the following is likely to be a limiting factor in quantifying phage persistence?

The lack of standardized phage preparations Signup and view all the answers

What statistical approach is suggested for the approval of biomedicine products like phages?

Statistical approaches that account for a range of possibilities Signup and view all the answers

What is one potential outcome if phage therapy is applied successfully?

Clearance of phage-susceptible bacteremia Signup and view all the answers

What is considered a major advantage of phage therapy compared to traditional antibiotic therapy?

Phage therapy offers relatively high speed and low cost of response to bacterial resistance. Signup and view all the answers

Which assumption is made about the clearance rate of phages in the context of phage therapy?

High clearance rates for all phages would render phage therapy ineffective. Signup and view all the answers

What is considered the key parameter that could enhance the success of phage therapy?

The rate of innate immune clearance of the inoculated phages. Signup and view all the answers

What was the primary method used to assess the persistence of phages in the study?

A controlled test involving a collection of phages and bacterial hosts. Signup and view all the answers

How did the blood titers of different phages vary after intraperitoneal injection in the study?

They varied greatly, by about 10,000×. Signup and view all the answers

Which of the following phages exhibited relatively high persistence according to the study?

Phage T3 Signup and view all the answers

What is one implication of the research findings regarding phage therapy?

Phages can sometimes enhance innate immune clearing of bacteria. Signup and view all the answers

What consideration is suggested regarding detailed knowledge of innate immunity pathways in phage therapy?

It is better if phage therapy does not depend on detailed knowledge of these pathways. Signup and view all the answers

What was the purpose of adding an extract of uninfected host cells to phage GH?

To recover the high persistence phenotype of phage GH Signup and view all the answers

What does the term 'persistence' refer to concerning phage GH?

The longevity and activity of phage in a host environment Signup and view all the answers

Which method was used to clarify the extract of uninfected cells?

Centrifugation at 10,000 rpm for 10 minutes Signup and view all the answers

What effect did the host extract have on low-persistence phage 0105phi7-2 when combined with phage GH?

It increased the persistence of phage 0105phi7-2 Signup and view all the answers

What does Rφ represent in the context of phage therapy?

The ratio of plaque-forming units in blood Signup and view all the answers

During which process was phage GH found to lose its high persistence?

Rate zonal centrifugation Signup and view all the answers

How did the persistence of host extract-boosted phage GH compare to unaltered phage G?

It showed a significant increase in persistence Signup and view all the answers

What was used to lyse the cells of the uninfected bacterial lawn?

Lysozyme Signup and view all the answers

Study Notes

Phage Therapy Advantages

Phage therapy offers a fast and cost-effective alternative to antibiotics in combating bacterial resistance.
Enhanced innate immune clearance of bacteria may improve the efficacy of phage therapy.

Immune Clearance and Persistence

High rates of innate immune clearance could limit the effectiveness of phage therapy.
However, some phages can boost immune clearance of bacteria, potentially aiding phage therapy outcomes.
A significant variance in the clearance rates of different phages suggests that targeting lower clearance rates may enhance effectiveness.

Research on Phage Persistence

A study tested four different phages' persistence in mouse blood, revealing a 10,000-fold difference in blood titers at 2-4 hours post-injection.
Phages T3 showed high persistence while phage T7 demonstrated low persistence.

Experimental Methodology

Experiments involved assessing bacterial lawns from Petri dishes and lysing them to examine phages’ effectiveness in circulation.
Uninfected bacterial lawns were harvested, mixed, and subjected to lysozyme treatment followed by freeze-thaw cycles for extraction.

Enhancements in Phage GH

A variant of phage G, named phage GH, exhibited high persistence dependent on a host factor.
Phage GH lost this persistence upon purification but could regain it when mixed with an extract from uninfected host cells.

Persistence Measurement

Persistence is defined as maintaining normalized phage titers (Rφ) above 0.03 for a minimum of 4 hours.
This level should suffice to clear bacteremia in a scenario of 10 million phages against 10 million bacteria per mL.

Implications for FDA Approval

Phage therapy, categorized under biomedicine, demands a reevaluation of approval strategies compared to traditional antibiotic therapies (chemo-medicine).
The approval process for phage therapy would need to consider the statistical nature and inherent variability of biological agents, similar to challenges faced in approving complex vaccines.
Historical precedents exist, such as the FDA approval of leech therapy, which highlight the complexities of biomedicine approvals.

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Description

This quiz explores the advantages of phage therapy over traditional antibiotic treatments in the context of rising bacterial resistance. It covers the implications of phage clearance rates in patient responses and the potential for improved therapeutic outcomes. Dive into the fascinating world of bacteriophages and their role in modern medicine.