A new methodology for rapidly measuring the level of antibiotic drug molecules in human blood serum has been developed, opening avenues to apply this technique in drug development and personalized medicine.
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.
AdvertisementAs 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.
The study has been published in journal Nature Nanotechnology.