Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Quantitative Approaches Provide New Perspective on Development of Antibiotic Resistance

29.11.2013
Using quantitative models of bacterial growth, a team of UC San Diego biophysicists has discovered the bizarre way by which antibiotic resistance allows bacteria to multiply in the presence of antibiotics, a growing health problem in hospitals and nursing homes across the United States.

Two months ago, the Centers for Disease Control and Prevention issued a sobering report estimating that antibiotic-resistant bacteria last year caused more than two million illnesses and approximately 23,000 deaths in the United States. Treating these infections, the report said, added $20 billion last year to our already overburdened health care system.


The researchers found a range of drug doses for which genetically identical bacterial cells exhibited drastically different behaviors: while a substantial fraction of cells stopped growing despite carrying the resistance gene, other cells continued to grow at a high rate—a phenomenon called “growth bistability.” Credit: J. Barrett Deris

Many approaches are now being employed by public health officials to limit the spread of antibiotic resistance in bacteria—such as limiting the use of antibiotics in livestock, controlling prescriptions of antibiotics and developing new drugs against bacteria already resistant to conventional drug treatments. But understanding how bacteria grow and evolve drug resistance could also help stop its spread by allowing scientists to target the process of evolution itself.

“Understanding how bacteria harboring antibiotic resistance grow in the presence of antibiotics is critical for predicting the spread and evolution of drug resistance,” the UC San Diego scientists say in an article published in the November 29 issue of the journal Science.

In their study, the researchers found that the expression of antibiotic resistance genes in strains of the model bacterium E. coli depends on a complex relationship between the bacterial colony’s growth status and the effectiveness of the resistance mechanism.

“In the course of developing complete resistance to a drug, a strain of bacteria often first acquires a mechanism with very limited efficacy,” says Terry Hwa, a professor of physics and biology who headed the research effort. “While much effort has been spent elucidating individually how a drug inhibits bacterial growth and how a resistance mechanism neutralizes the action of a drug, little is known previously about how the two play off of each other during the critical phase where drug resistance evolves towards full strength.”

According to Hwa, the interaction between drug and drug-resistance is complex because the degree of drug resistance expressed in a bacterium depends on its state of growth, which in turn depends on the efficacy of drug, with the latter depending on the expression of drug resistance itself. For a class of common drugs, the researchers realized that this chain of circular relations acted effectively to promote the efficacy of drug resistance for an intermediate range of drug doses.

The use of predictive quantitative models was instrumental in guiding the researchers to formulate critical experiments to dissect this complexity. In their experiments, E. coli cells possessing varying degrees of resistance to an antibiotic were grown in carefully controlled environments kept at different drug doses in “microfluidic” devices—which permitted the researchers to manipulate tiny amounts of fluid and allowed them to continuously observe the individual cells.

Hwa and his team found a range of drug doses for which genetically identical bacterial cells exhibited drastically different behaviors: while a substantial fraction of cells stopped growing despite carrying the resistance gene, other cells continued to grow at a high rate. This phenomenon, called “growth bistability,” occurred as quantitatively predicted by the researchers’ mathematical models, in terms of both the dependence on the drug dose, which is set by the environment, and on the degree of drug resistance a strain possesses, which is set by the genetic makeup of the strain and is subject to change during evolution.

“Exposing this behavior generates insight into the evolution of drug resistance,” says Hwa. “With this model we can chart how resistance is picked up and evaluate quantitatively the efficacy of a drug.” However, this model has only been established for one class of drugs and one class of drug-resistance mechanisms. Hwa believes it is important to establish such predictive models for all the common drugs in pathogenic bacterial species.

“My hope,” he adds, “is to get the message out to drug companies and hospitals that there is an informative, quantitative way to look at the action of a drug on bacteria and at the consequences of using a drug on bacteria as they try to pick up resistance, and that this approach can be incorporated in both the design and evaluation of drug efficacy in clinically relevant settings.”

Hwa says the principle of interaction between drug and drug-resistance is important to understand not only for the evolution of antibiotics, but also for the emergence of drug resistance in other diseases. A prominent example is the rapid emergence of cancer lines resistant to drug treatment, which underlies most failures in cancer drug therapies. While there are obviously numerous differences between the evolution of drug resistance in bacteria and in cancer, Hwa noted that the connection between the two was sufficient to motivate the Physical Science-Oncology program of the National Cancer Institute to co-sponsor this study.

Other UC San Diego scientists involved in the discovery were J. Barrett Deris, Minsu Kim, Zhongge Zhang, Hiroyuki Okano, Rutger Hermsen and Alexander Groisman, an associate professor of physics at UC San Diego. Funding for the study was provided by the National Institutes of Health and the National Science Foundation.

Media Contact
Kim McDonald, 858-534-7572, kmcdonald@ucsd.edu

Kim McDonald | EurekAlert!
Further information:
http://www.ucsd.edu
http://ucsdnews.ucsd.edu/pressrelease/quantitative_approaches_provide_new_perspective_on_development_of_antibioti

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Supersensitive through quantum entanglement

28.06.2017 | Physics and Astronomy

X-ray photoelectron spectroscopy under real ambient pressure conditions

28.06.2017 | Physics and Astronomy

Mice provide insight into genetics of autism spectrum disorders

28.06.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>