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Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Concept of Darwinian fitness
- The importance of the fitness impact
- Predicting the future of drug resistance
- Drug resistant bacteria are less fit
- Erythromycin resistance
- Sulphonamide resistance
- Reversal of drug resistance
- How to measure fitness?
- Competitive fitness assay
- The molecular epidemiology approach
- Transmission of drug resistant M. tuberculosis
- Evolution of drug resistance
- Effect of drug resistance mutations
- Measuring the fitness impact of drug mutations
- Selection of spontaneous drug resistant mutants
- Clinical isolates from patients
- Rifampicin resistance in M. tuberculusis
- Some clinical mutants have no fitness defect
- Clinical frequency of rpoB mutations
- Isoniazid resistant M. tuberculosis
- Virulence effects of KatG mutations
- Epidemiological study in San Francisco
- Environment effects of fitness measurements
- In vitro vs. in vivo fitness
- Effect of strain genetic background
- In vivo fitness of FQR C. jejuni
- Pre-adapted strain families?
- Biogeography of M. tuberculosis
- Association of Mtb - 'Beijing' with MDR
- Compensatory evolution
- Experimental evidence
- Compensatory evolution in resistant E. coli
- Effect of compensation
- Compensation is more likely than reversion
- Types of compensatory mutations
- Environment effects on compensation
- Questions for future research
- Clinical relevance of compensation
- MDR TB and XTR TB
- Comparative genomics of different strains
- Summary
- Acknowledgements
Topics Covered
- Concept of Darwinian fitness
- Understanding the fitness impact of drug resistance
- Mathematical models
- Reversal of drug resistance in bacteria
- How to measure fitness
- The molecular epidemiology approach
- Effect of drug resistance mutations
- Environment effects on fitness measurements
- Effect of strain genetic background
- Pre-adapted strain "families"
- Biogeography of M. tuberculosis
- Compensatory evolution
- Experimental evidence
- Compensation prevents reversion to drug sensitivity
- Types of compensatory mutations
- Questions for future research
- Comparative genomics
Links
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Talk Citation
Gagneux, S. (2016, February 26). Fitness and compensation [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 3, 2024, from https://doi.org/10.69645/WZAL9088.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Sébastian Gagneux has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Pharmaceutical Sciences
Transcript
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0:00
Hello. My name is Sebastien Gagneux and I am
a group leader at the MRC National Institute for Medical Research in London.
I'm going to talk about the role of Darwinian fitness and
compensation in the evolution of drug resistance in bacteria.
0:19
I would like to start this presentation by introducing
the concept of Darwinian fitness in the context of antibiotic resistance.
I will then outline why we should care about the role of
Darwinian fitness in drug resistance and present several ways fitness can be measured.
I will discuss how the fitness of drug-resistant bacteria
can vary depending on the particular drug resistance mutation,
the environment, or strain genetic background.
And we'll review various aspects of compensatory evolution and
end with a few suggestions for future research.
0:59
Darwinian fitness can broadly be defined as
the ability of an organism to survive and reproduce in a given environment.
In addition to measuring the total or absolute number of viable offsprings,
Darwinian fitness is often expressed as a relative measure.
For example, as the relative fitness of
a drug-resistant organism compared to the corresponding drug-susceptible form.
1:25
There are at least four main reasons why we should
care about the effects of drug resistance in bacterial fitness.
First, we would like to be able to make predictions about
the future trajectory of the global epidemic of drug resistance,
and I will show you an example of that.
Second, we need to be able to evaluate
interventions aimed at reducing the spread of drug-resistant organisms.
For example, will the withdrawal of
a particular antibiotic result in the reduction of resistance?
Third, a better knowledge of the fitness impact of
drug resistance could help us design better antimicrobials.
For example, by focusing on compounds to which developing resistance to,
will be particularly costly to the pathogen.
And four, studying fitness in the context of drug resistance
allows us to address fundamental evolutionary questions.