Nutrition 6: Antibiotic development

Question 1

What are the issues around of antibiotics

Answer 1

Antibiotics are effective and reduce deaths.

However not everyone has timely access to antibiotics. and the use of antibiotics can be reduced by increasing vaccines

Question 2

When was the innovation gap and what does it mean

Answer 2

From 1940-1960 = golden age of discovery from bacterial compounds to get antibiotics. Between 1962 to 2000 there were no major classes of antibiotics introduced.

Question 3

What is the ideal antibiotic

Answer 3

• Tight binding to target,
• inexpensive to mass produce, -Stable for transportation
• low toxicity- easily secreted
• low ability to induce resistance
• Easily degraded
• Low dose that is effective but not toxic
• Good circulation within the body.
• Well absorbed by bacteria
• Broad spectrum (gram + and -)
• Not affect beneficial microbes

Question 4

What is one way that B lactamase using bacteria can be defeated

Answer 4

Create a competitive inhibitor (clavulanic acid) for the B-lactamase enzyme which wants to inactivate it. As it doesn’t have an antibiotic activity itself, B lactamase is inhibited and penicillin is able to work.

Question 5

What are the characteristics of different modifications of the common antibiotic structures

Answer 5

There is a modification to the synthetic scaffold of classes of the original molecule to make different generations.
Changes the way that AB interacts with the target to overcome resistance

Question 6

What is the two different modifications of chemical scaffold.

Answer 6

1. Modify the way it binds to its target or

2. Modify it so that it opposes the way that bacteria resists it

Question 7

What is identification of new antibiotic scaffolds through searches of underexplored ecological niches and bacterial

Answer 7

Looking at plants, marine life and swamp dwellers. Looking at isolated
bacteria populations.

Question 8

What is Bioinformatic analysis of bacterial genomes

Answer 8

Looking at silent genome sequences in bacteria that could produce products that could be used to kill bacteria

Question 9

What are AMPS (antimicrobial peptides) and what is good and bad

Answer 9

AMPS are lipopeptides that physically insert into the bacterial membrane
Problems is that they are not as stable
Solution:
Potentially nanoparticles made of AMPlike peptides could enhance activity by increasing multivalent interacts

Question 10

What are SNaPPS (Structurally nanoengineered antimicrobial peptide polymers) as a mode of antibiotic

Answer 10

They have multimodal mechanism of bacterial cell death by outer membrane destabilisation, unregulated ion movement across the cytoplasm membrane and induction of the apoptotic like death pathway. good for gram - bacteria

Question 11

What is the business model leading to lack of antibiotics

Answer 11

They are a losing proposition for drug companies as the market for new antibiotics is small because you don’t want to release them unless necessary but you still need a lot for backup

Question 12

What are the 3 strategies to overcome AB resistance in bacteria

Answer 12

1. modification of common core structures of different antibiotic classes using medicinal chemistry
2. the identification of new antibiotic scaffolds through searches of unexplored ecological niches and bacterial taxa
3. Bioinformatic analysis of bacterial genome

Question 13

What is good about

Answer 13

Active against Gram positive and negative bacteria, there is lack of cross resistance to existing drugs and able to be tailored synthetic