Classic reaction kinetics can explain complex patterns of antibiotic action
Event details
| Date | 04.11.2014 |
| Hour | 12:15 |
| Speaker | Dr. Pia zur Wiesch, Harvard University |
| Location | |
| Category | Conferences - Seminars |
Finding optimal dosing strategies for treating bacterial infections (e.g. dosing frequency, dose levels, and duration of therapy) is extremely difficult, and improving therapy requires costly and time-intensive experiments. Quantitative predictions of drug-mediated bacterial killing would enable rational design of antibiotic treatment strategies. However, this requires a better mechanistic explanation of drug effects. Three poorly understood phenomena complicate predictions of antibiotic activity: post-antibiotic growth suppression, density-dependent antibiotic effects. and persister cell formation. Here, we show that chemical binding kinetics alone are sufficient to explain these three phenomena, using single-cell data and time-kill curves of Escherichia coli and Vibrio cholerae exposed to a variety of antibiotics in combination with a novel theoretical model.
This work provides a parsimonious mechanistic explanation for all three phenomena. Our model reproduces existing observations, has a high predictive power across different experimental setups, and makes several testable predictions, which we were able to verify in new experiments. While a variety of biological mechanisms have previously been invoked to explain post-antibiotic growth suppression, 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" -based approach should provide insight for more rapid and cheaper development of new strategies for antibiotic and other chemotherapeutic regimens.
Bio: Research Fellow
Yale School of Public Health
September 2014 – Present (2 months)New Haven, CT
Harvard Medical School
Research Fellow
April 2012 – August 2014 (2 years 5 months)
ETH Zurich
Postdoctoral Fellow
May 2011 – March 2012 (11 months)Zurich
ETH Zurich
Research Assistant
October 2007 – April 2011 (3 years 7 months)Zurich
World Health Organization
Intern
August 2007 – September 2007 (2 months)Bonn Area, Germany
Roche Diagnostics
Research Assistant
April 2007 – August 2007 (5 months)Mannheim Area, Germany
Assistant at International Office
Christian-Albrechts-Universität Kiel
July 2001 – April 2003 (1 year 10 months)Kiel Area, Germany
This work provides a parsimonious mechanistic explanation for all three phenomena. Our model reproduces existing observations, has a high predictive power across different experimental setups, and makes several testable predictions, which we were able to verify in new experiments. While a variety of biological mechanisms have previously been invoked to explain post-antibiotic growth suppression, 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" -based approach should provide insight for more rapid and cheaper development of new strategies for antibiotic and other chemotherapeutic regimens.
Bio: Research Fellow
Yale School of Public Health
September 2014 – Present (2 months)New Haven, CT
Harvard Medical School
Research Fellow
April 2012 – August 2014 (2 years 5 months)
ETH Zurich
Postdoctoral Fellow
May 2011 – March 2012 (11 months)Zurich
ETH Zurich
Research Assistant
October 2007 – April 2011 (3 years 7 months)Zurich
World Health Organization
Intern
August 2007 – September 2007 (2 months)Bonn Area, Germany
Roche Diagnostics
Research Assistant
April 2007 – August 2007 (5 months)Mannheim Area, Germany
Assistant at International Office
Christian-Albrechts-Universität Kiel
July 2001 – April 2003 (1 year 10 months)Kiel Area, Germany
Practical information
- Informed public
- Free
Organizer
- UPKIN, Laboratory of Microbiology and Microsystems