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SUMMARY:Classic reaction kinetics can explain complex patterns of antibiot
 ic action
DTSTART:20141104T121500
DTSTAMP:20260407T105413Z
UID:28ed1ebeb7301854012e4ed8040122c9576b8f05d942575a2f80e628
CATEGORIES:Conferences - Seminars
DESCRIPTION:Dr. Pia zur Wiesch\, Harvard University\nFinding optimal dosin
 g strategies for treating bacterial infections (e.g. dosing frequency\, do
 se levels\, and duration of therapy) is extremely difficult\, and improvin
 g therapy requires costly and time-intensive experiments. Quantitative pre
 dictions of drug-mediated bacterial killing would enable rational design o
 f antibiotic treatment strategies. However\, this requires a better mechan
 istic explanation of drug effects. Three poorly understood phenomena compl
 icate predictions of antibiotic activity: post-antibiotic growth suppressi
 on\, density-dependent antibiotic effects. and persister cell formation. H
 ere\, we show that chemical binding kinetics alone are sufficient to expla
 in these three phenomena\, using single-cell data and time-kill curves of 
 Escherichia coli and Vibrio cholerae exposed to a variety of antibiotics i
 n combination with a novel theoretical model.\nThis work provides a parsim
 onious mechanistic explanation for all three phenomena. Our model reproduc
 es existing observations\, has a high predictive power across different ex
 perimental setups\, and makes several testable predictions\, which we were
  able to verify in new experiments. While a variety of biological mechanis
 ms have previously been invoked to explain post-antibiotic growth suppress
 ion\, density-dependent antibiotic effects\, and especially persister cell
  formation\, our findings reveal that a simple model which considers only 
 binding kinetics provides a unifying explanation for these three complex\,
  phenotypically distinct behaviours. This "chemical reaction kinetics" -ba
 sed approach should provide insight for more rapid and cheaper development
  of new strategies for antibiotic and other chemotherapeutic regimens.\nBi
 o: Research Fellow\nYale School of Public Health\nSeptember 2014 – Prese
 nt (2 months)New Haven\, CT\nHarvard Medical School\nResearch Fellow\nApri
 l 2012 – August 2014 (2 years 5 months)\nETH Zurich\nPostdoctoral Fellow
 \nMay 2011 – March 2012 (11 months)Zurich\nETH Zurich\nResearch Assistan
 t\nOctober 2007 – April 2011 (3 years 7 months)Zurich\nWorld Health Orga
 nization\nIntern\nAugust 2007 – September 2007 (2 months)Bonn Area\, Ger
 many\nRoche Diagnostics\nResearch Assistant\nApril 2007 – August 2007 (5
  months)Mannheim Area\, Germany\nAssistant at International Office\nChrist
 ian-Albrechts-Universität Kiel\nJuly 2001 – April 2003 (1 year 10 month
 s)Kiel Area\, Germany
LOCATION:SV 1717a http://map.epfl.ch/?room=sv1717a
STATUS:CONFIRMED
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