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SUMMARY:Observations of a mathematician running a wet-lab: decades of phar
 macology\, MICs\, efflux pumps\, drug interactions and antibiotic resistan
 ce in the context of models and genomics - Prof Robert Beardmore (Exeter U
 niversity)
DTSTART:20130201T140000Z
DTEND:20130201T150000Z
UID:TALK43275@talks.cam.ac.uk
CONTACT:Shery Huang
DESCRIPTION:The principles for treatment with antibiotics were laid down o
 ver a century ago\, well before\, even\, the discovery of antibiotics and 
 before we knew much of the mechanisms of inheritance in evolution. Alexand
 er Flemming knew about penicillin resistance and said that the problem wit
 h treatment was the "...danger that the ignorant man may easily underdose 
 himself and\, by exposing his microbes to non-lethal quantities of the dru
 g\, make them resistant."\n\nThis quote embodies the principle of "hit ear
 ly\, hit hard" already described as the "old therapeutic remedy" by Paul E
 rlich in 1913. So\, as the use of drug combinations is a natural extension
  of the hit-hard logic\, we take a closer look at synergistic drug combina
 tions in the lab and ask\, is it true that harsher\ntherapies necessary re
 duce bacterial load?\n\nThe answer\, at least for the two translational in
 hibitors we tested in vitro using E.coli is 'no'. We'll even show data ind
 icating that synergistic drugs can lose out in the lab to treatments that 
 rotate between the same drug pair\, despite the presence of a fast-acting\
 , cross-resistance operon.\n\nThe reason: selection for resistance is grea
 ter for harsher therapies and as tests for drug efficacy usually only last
  a day\, much shorter than the length of exposure commonly found in clinic
 al therapy\, common pharmacological measures of drug efficacy miss feature
 s of drug-resistance adaptation that can occur within tens of bacterial ge
 nerations.
LOCATION:Small Lecture Theatre\, Cavendish Laboratory
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