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 firstname.lastname@example.org.
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!
Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto
Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy