Emergent Infections

Question 1

What defines an emerging pathogen?

Answer 1

• A previously unknown organism that causes disease OR
• A previously identified organism that has recently acquired the capacity to cause disease OR
• A previously identified pathogen that has recently acquired the capacity to resist antibiotic treatment

Question 2

What are the 3 factors that contribute to the emergence of infectious disease?

Answer 2

1. Human demographics of increasing population
2. Overuse of antibiotics in agriculture
3. Land use crowding and movement due to war has cause spread of disease

Question 3

How can incorrect drug therapy lead to antibiotic resistance?

Answer 3

Low dose of drug permits bacterial replication. The presence of drug provides modest levels of selection which result in evolution of drug resistance.

Question 4

How does selection increase the rate of acquisition of antibiotic resistance?

Answer 4

Mutations are sporadic in the bacterial population and mutations that are helpful against antibiotics are likely already present in the population, but without the selection pressure of antibiotics, these traits are not necessarily retained in the population.

Question 5

How does P. aeruginosa infection in a CF lung can lead to rapid evolution of resistance?

Answer 5

It creates a state of hypermutation as the CF causes many different niches in the lung to be created where there may be a different amount of drug reaching each area and this variety of selections pressures greatly increases the chance that the bacteria will hit the “sweet spot” of antibiotic resistance.

Question 6

How does the multi drug efflux system confer antibiotic resistance?

Answer 6

Modification of them via mutation can make them non-selective which can cause efflux of a variety of drugs causing multi drug resistance to multiple antibiotics in a short amount of time.

Question 7

How can we force there to be decreased lethality in pathogens with abiotic vectors?

Answer 7

By denial of a non-living vector route for transmission we can force the pathogen to use living hosts where high lethality wouldn’t be favorable for their own survival, causing selection away from high lethality.

Question 8

What is the reductionist approach to drug discovery?

Answer 8

1. Identify molecular mechanisms of disease (i.e. virulence factors).
2. Design drugs to target virulence factors identified by experiment (rational drug design).

Question 9

What is the genomic approach to drug discovery?

Answer 9

1. Sequence the genome of the pathogen.

2. Design drugs to target all potential virulence factors.

Question 10

What is the new “attack intrinsic resistance” approach to drug discovery?

Answer 10

1. Identify and analyze mechanisms of resistance (stationary phase, biofilms, efflux pumps).
2. Ensure that candidate lead compounds work in spite of mechanisms of resistance BEFORE the compound is seriously considered for R&D.
3. Design drugs to attack the resistance mechanism