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Automated Device Created That Improves Understanding Of How Antibiotic Resistance Evolves At The Genetic Level

With the discovery of antibiotics, medicine acquired power on a scale never before possible to protect health, save lives, and reduce suffering caused by certain . But the power of antibiotics is now under siege because some virulent infections no longer respond to antibiotic drugs.

This antibiotic resistance is an urgent public health threat that a team of researchers from in Istanbul, , and and in Cambridge, Mass., aim to stop. Their approach is based on an automated device they created that yields a new understanding of how antibiotic resistance evolves at the genetic level. The team will present its work at the 57th Annual Meeting of the (BPS), held Feb. 2-6, 2013, in Philadelphia, Pa.

Called the “morbidostat,” the device grows bacteria in various concentrations of antibiotic. This enabled researchers to identify the concentrations at which the antibiotics stopped working and the bacteria became resistant to therapy. Next, they targeted key genes involved in creating the drug-resistant states. Their approach documented real-time changes in genes that gave bacteria an advantage in evolving to “outwit” antibiotics.

Knowledge at the gene level can be applied to the molecular design of the next generation of bacteria-killing antibiotics.

“Morbidostat is designed to evolve bacteria in conditions comparable with clinical settings,” explains Erdal Toprak of Sabanci University. “Combined with next generation genome sequencing technologies, it is possible to follow the evolution of resistance in real time and identify resistance-conferring genetic changes that accumulate in the bacterial genome.”

Data show an unusual survival profile of the common bacteria they used, Escherichia coli. “We identified striking features in the evolution of resistance to the antibiotic trimethoprim,” Toprak says. It was these unusual features that helped them isolate the gene involved in conferring antibiotic resistance through multiple mutations.

The team’s next steps will involve determining how this genetic information might one day be applied to drug design to develop new antibiotic therapies.


Presentation #3390-Pos, “Evolution of antibiotic resistance through a multi-peaked adaptive landscape,” will take place at 10:30 a.m. on Wednesday, Feb. 6, 2013, in the Pennsylvania Convention Center, Hall C. ABSTRACT: http://tinyurl.com/bfcke65

This news release was prepared for the Biophysical Society (BPS) by the American Institute of Physics (AIP).

The 57th Annual Meeting will be held at the Pennsylvania Convention Center (1101 Arch Street, Philadelphia, PA 19107). For maps and directions, please visit: http://www.paconvention.com/explore- philadelphia/directions-and-parkingg.


Meeting Home Page: http://www.biophysics.org/2013meeting/Main/tabid/35 23/Default.aspx

Housing and Travel Information: http://www.biophysics.org/2013meeting/Accommodation sTravel/HotelInformation/tabid/3621/Default.aspx

Program Abstracts and Itinerary Planner: http://www.abstractsonline.com/plan/start.aspx? mkey=%7B763246BB-EBE4-430F-9545-81BC84D0C68C%7D

American Institute of Physics