The study, published today in Nature Nanotechnology, describes the exploitation of a sensor for measuring the concentration of effective antibiotics in blood, giving an indication of their efficiency against disease causing pathogens, for instance multidrug resistant hospital "superbugs".
This development could potentially give a far greater understanding of the effectiveness of drug dosages required for different individuals, reducing potential toxic effects, allowing personalised treatment for patients and leading to new insights into optimal clinical regimes, such as combination therapies.
When effective, antibiotic molecules impose cellular stress on a pathogen's cell wall target, such as a bacterium, which contributes to its breakdown. However, competing molecules in solution, for example serum proteins, can affect the binding of the antibiotic to the bacterium, reducing the efficacy of the drug. Serum proteins bind to drugs in blood and, in doing so, reduce the amount of a drug present and its penetration into cell tissues.
As the amount of antibiotics that bind to serum proteins will vary between individuals, it is extremely valuable to be able to determine the precise amount of the drug that is bound to serum proteins, and how much is free in the blood, in order to be able to accurately calculate the optimum dosage.
Existing biosensors on the market do not measure cellular stress, however, the nanomechanical sensor exploited by a group of researchers from the London Centre for Nanotechnology (LCN) at UCL, the University of Cambridge, the University of Queensland and Jomo Kenyatta University of Agriculture and Technology, can accurately measure this important information even when antibiotic drug molecules are only present at very low concentrations.
The researchers coated the surface of a nanomechanical cantilever array with a model bacterial membrane and used this as a surface stress sensor. The sensor is extremely sensitive to tiny bending signals caused by its interactions with the antibiotics, in this case, the FDA-approved vancomycin and the yet to be approved oritavancin, which appears to deal with certain vancomycin-resistant bacteria, in the blood serum.
This investigation has yielded the first experimental evidence that drug-serum complexes (the antibiotics bound to the competing serum proteins) do not induce stress on the bacteria and so could provide realistic in-vitro susceptibility tests for drugs and to define effective doses which are effective enough but less toxic to patients.
In the future, the researchers believe that with a suitably engineered surface probe, this sensor could be paired with customised drug delivery for anaesthetics, anti-cancer, anti-HIV and antibacterial therapies.
The lead author of the study, Dr. Joseph W. Ndieyira of the LCN, said "This discovery represents a major advance in our fundamental understanding of the pathways between chemical and mechanical signals in a complex media, such as blood serum, and how this information can be used to tune the efficacy of drugs and to minimise the potential toxic side effects."
Dr. Ndieyira added, "Monitoring the levels of active free drugs in serum can be crucial in honing therapeutic solutions for patients to enhance drug administration. This will be particularly helpful in addressing problems of drugs which have to be used in very precise quantities and where there are large differences in how drugs affect individuals and groups. For example, overuse of antibiotics can fuel resistance to drugs or underuse of anaesthetics may lead to a patient regaining consciousness during an operation."
Notes to editors
1. For more information or to speak to one of the researchers, please contact Dominique Fourniol in the UCL Media Relations Office on tel: +44 (0)20 3108 3843, out of hours +44 (0)7917 271 364, e-mail: email@example.com
2. Surface-stress sensors for rapid and ultrasensitive detection of active free drugs in human serum is published online in Nature Nanotechnology on 2 March 2014.
3. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.
About UCL (University College London)
Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender and the first to provide systematic teaching of law, architecture and medicine.
We are among the world's top universities, as reflected by our performance in a range of international rankings and tables. According to the Thomson Scientific Citation Index, UCL is the second most highly cited European university and the 15th most highly cited in the world.
UCL has nearly 27,000 students from 150 countries and more than 9,000 employees, of whom one third are from outside the UK. The university is based in Bloomsbury in the heart of London, but also has two international campuses – UCL Australia and UCL Qatar. Our annual income is more than £800 million.
Dominique Fourniol | EurekAlert!
An ounce of prevention: Research advances on 'scourge' of transplant wards
28.08.2015 | University of Wisconsin-Madison
Hypoallergenic parks: Coming soon?
27.08.2015 | American Society of Agronomy
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.
These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...
Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.
For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...
It comes when called, bringing care utensils with it and recording how they are used: Fraunhofer IPA is developing an intelligent care cart that provides care staff with physical and informational support in their day-to-day work. The scientists at Fraunhofer IPA have now completed a first prototype. In doing so, they are continuing in their efforts to improve working conditions in the care sector and are developing solutions designed to address the challenges of demographic change.
Technical assistance systems can improve the difficult working conditions in residential nursing homes and hospitals by helping the staff in their work and...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
31.08.2015 | Earth Sciences
28.08.2015 | Physics and Astronomy
28.08.2015 | Health and Medicine