F11 Antibiotic resistance

Question 1

How should a ’super antibiotic’ look like?

Answer 1

many requirements, including:
• broad activity spectrum
• active against biofilms
• very low concentrations needed
• acts on multiple, unrelated, essential bacterial targets (low resistance)
• structural targets are often superior to single protein targets
• safe for humans / little side effects

Question 2

medicinal honey

Answer 2

• broad activity spectrum
• active against biofilms
• very low concentrations needed
• excellent adhesion to wounds
• safe
• renewable resource (save the bees!)

A combination of different molecules and factors with different mechanisms!
-> acts on multiple, unrelated, essential bacterial targets incl. structural targets

Question 3

Antimicrobial peptides

Answer 3

• in all domains of life
• multiple complex mechanisms
• very little resistance
• antibacterial, antiviral, antifungal…
• very interesting for further research!

Question 4

new multi target approaches

Answer 4

multi-effect
multi-target
combination therapy

Question 5

intrinsic multiple effects, + och -

Answer 5

+
• only one drug needs to be administered
• can have highly specific target binding
• kill rapidly

-
• target mutation may occur fast (structural targets more
favorable than enzymes)

Question 6

multiple independent targets, + och -

Answer 6

+
• only one drug needs to be administered
• often kill rapidly
• resistance develops slower, since two independent target
mutations are needed

-
• target binding may be less specific

Question 7

combination approaches, + och -

Answer 7

\+
• lower doses 
• specific target binding 
• killing kinetics depend on combination 
• resistance-breaking

-
• two drugs need to be administered
• resistance development may be slowed, but if resistance against one component occurs, the second one may become ineffective as well

Question 8

Novel combination approaches: What’s in the pipeline?

Answer 8

Resistance breakers: inactivating intrinsic resistance mechanisms

permeabilizers
sensitizers
efflux pumps inhibitors
biofilm inhibitors