Theory 14/Life, Medicine & Mind /Microbial physiology
Persisters Tune to Treatment
Persistence is treated as a fixed proportion. It may be a dial set by the environment.
The persister fraction in a bacterial population is tuned to the duration of antibiotic exposure rather than being a fixed bet-hedging fraction, so longer courses select for higher persistence.
01The evidence
Persister fractions vary between isolates and change after exposure, which is inconsistent with a fixed fraction.
02The tension
Bet-hedging models predict a fraction set by the statistics of the environment. Treatment duration is part of that statistics but is not modelled.
03The mechanism
The optimum persister fraction depends on how long a lethal episode lasts. If episodes are long, more persisters are favoured because survivors repopulate.
That makes duration the selector, and predicts that repeated long courses should raise the persister fraction.
04What this is not
Fixed models predict a constant. This predicts adaptation to course length.
05Predictions
- P1Persister fraction should rise with course length.
- P2Shorter courses should reduce it.
- P3The fraction should revert without exposure.
06Refutation
A constant fraction across course lengths would favour fixed bet hedging.
07What it changes
It would support shorter antibiotic courses.