But what if it doesn't have to be that way?
In a presentation at the American Society for Biochemistry and Molecular Biology's annual meeting, titled "Driving backwards the evolution of antibiotic resistance," Harvard researcher Roy Kishony will discuss his recent work showing that some drug combinations can stop or even reverse the normal trend, favoring bacteria that do not develop resistance. The talk will be in Anaheim Convention Center Room 304D, on Sunday April 25 at 3:30 pm PST.
"Normally, when clinicians administer a multi-drug regimen, they do so because the drugs act synergistically and speed up bacterial killing," Kishony explains. However, Kishony's laboratory has focused on the opposite phenomenon: antibiotic interactions that have a suppressive effect, namely when the combined inhibitory effect of using the two drugs together is weaker than that of one of the drugs alone.
Kishony and his team identified the suppressive interaction in E. coli, discovering that a combination of tetracycline – which prevents bacteria from making proteins – and ciprofloxacin – which prevents them from copying their DNA – was not as good as slowing down bacterial growth as one of the antibiotics (ciprofloxacin) by itself.
Kishony notes that this suppressive interaction can halt bacterial evolution, because any bacteria that develop a resistance to tetracycline will lose its suppressive effect against ciprofloxacin and die off; therefore, in a population the bacteria that remain non-resistant become the dominant strain.
While such a weakened antibiotic combination is not great from a clinical standpoint, the Kishony lab is using this discovery to set up a drug screening system that could identify novel drug combinations that could hinder the development of resistance but still act highly effectively. "Typical drug searches look for absolute killing effects, and choose the strongest candidates," he says. "Our approach is going to ask how these drugs affect the competition between resistant versus sensitive bacterial strains."
To develop such a screen, Kishony and his group first had to figure how this unusual interaction works.
"Fast growing bacteria like E. coli are optimized to balance their protein and DNA activity to grow and divide as quickly as the surrounding environment allows," Kishony explains. "However, when we exposed E. coli to the ciprofloxacin, we found that their optimization disappeared."
"We expected that since the bacteria would have more difficulty copying DNA, they would slow down their protein synthesis, too," Kishony continues. "But they didn't; they kept churning out proteins, which only added to their stress." However, once they added the tetracycline and protein synthesis was also reduced in the E. coli, they actually grew better than before. They then confirmed the idea that production of ribosomes - the cell components that make proteins - is too high under DNA stress by engineering E. coli strains that have fewer ribosomes than regular bacteria. While these mutants grew a more slowly in normal conditions, they grew faster under ciprofloxacin inhibition of DNA synthesis.
Kishony notes that their preliminary work on the development of a screen for drugs that put resistance in a disadvantage looks promising, and hopes that it would lead to the identification of novel drugs that select against resistance.
NOTE TO EDITORS: The American Society for Biochemistry and Molecular Biology annual meeting is part of the Experimental Biology 2010 conference that will be held April 24-28, 2010 at the Anaheim Convention Center. The press is invited to attend or to make an appointment to interview Dr. Kishony. Please contact Nicole Kresge at 202.316.5447 or email@example.com.
The American Society for Biochemistry and Molecular Biology (www.asbmb.org) is a nonprofit scientific and educational organization with over 12,000 members. Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of scientific and educational journals: the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific workforce.
Nicole Kresge | EurekAlert!
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences