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Combating Antibiotic Resistance

Summary

A Paradigm Shift in Addressing Antimicrobial Resistance: Measuring the Transition Between Antibiotic Susceptibility and Resistance

 

With the exception of our own immune systems, antibiotics are our only line of defense in the fight against micro-organism-based infectious disease. However, microbes have acquired resistance mechanisms to every class of antibiotics that are currently available. Exacerbating this problem is the fact that, over the last 30 years, no major new types of antibiotics have been developed; partly because large pharma companies don't have the proper incentives to direct valuable resources toward the development of novel antimicrobials that will likely be rendered ineffective in a relatively short period of time due to acquired resistance. Also contributing towards the emergence and spread of antibiotic resistance is the misuse and overuse of antibiotics in the clinic and on the farm.

The evolution of resistant strains is a natural phenomenon that occurs due to spontaneous mutations that are acquired during DNA replication as well as the acquisition of resistance determinants (genes) by horizontal gene transfer and/or recombination. As new resistance mechanisms emerge, they quickly spread globally and compromise our ability to treat common infectious diseases.

Description

We are developing in vitro systems to generate controlled chemical and community environments that mimic the features of real-world that are important determinants for evolutionary rate and resistance potential. In addition, we are developing tools to isolate and analyze single bacteria along the transition pathway towards the antibiotic resistant state. Based on these measurements, we will develop new metrics to quantitatively predict the onset of the resistance transition.

These measurement tools will allow us to predict the potential for emergence of resistance to traditional and novel antimicrobial therapies.  In doing so, pharma companies can make more informed decisions on rational drug design strategies. And finally, the availability of a "resistance potential" metric will allow for better decision making in the clinic and by regulatory agencies that deem when and how a particular antibiotic should be utilized.

 

 

Created May 10, 2016, Updated September 21, 2016