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New Method Evaluates Antibiotics Based on the Tiny Vibrations of Dying Microbes

The NIST-developed technique could greatly speed up the process of diagnosing infections.
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Researchers have devised a way of classifying bacteria based on how it vibrates, according to a paper published in Scientific Reports. The technique, which relies on ultrasensitive piezoelectric sensors, makes it possible to determine the appropriate antibiotics to treat an infection in less than one hour.

Understand that when it comes to infections, timing is a big problem. The symptoms of an infection might look the same for a whole lot of different varieties of bacteria, many of which respond differently to different antibiotics. Classifying the bacterial culprit behind an infection is usually a matter of taking a sampling of bacterial cells, tossing them in a dish, and then waiting for them to multiply to the point that it's possible to start testing out different antibiotics on the accumulated cells (or culture). This is called antimicrobial susceptibility testing (AST).

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The problem is that this takes time. Usually, patients are treated with antibiotics immediately rather than waiting around for a culture to complete. This is a process of guesswork and the result is often antibiotic overtreatment. Patients are often given broad-spectrum antibiotics to treat infections caused by bacteria that might be knocked easily with a more limited antibiotic. Overuse of broad-spectrum antibiotics have several negative consequences, including increasing rates of antibiotic resistance.

The ideal would be a way of classifying bacteria without having to wait around for several days (in some cases) for a culture to develop. This is where the new method developed by Ward Johnson and his team at the National Institute of Standards and Technology (NIST) comes in. The approach is based on "rapidly sensing mechanical fluctuations of bacteria and the effects of antibiotics on these fluctuations," according to the paper. Basically, different varieties of bacteria have their own intrinsic vibrations and we now have sensors sensitive enough pick up these movements and how those movements change in the presence of different antibiotics.

The technique involves taking some bacteria and smearing them all over a thin quartz disc, which is connected to a pair of electrodes, making it an electronic bridge. An electrical signal is then sent across the disc, or resonator, at a frequency approaching the natural resonant frequency of the quartz crystal. The bacteria, meanwhile, change this resonant frequency, with the result being signal noise between the input electrical signal and the bacteria-tweaked resonant frequency of the quartz. This noise is registered in the output signal from the bridge.

Johnson and co. did experiments using E. coli bacteria and its nemesis, the antibiotic polymyxin. After coating the quartz disc in bacteria and observing the expected signal noise, they then administered the antibiotic. Within seven minutes, the noise dropped to near-zero. Repeating the experiment with a different antibiotic, ampicillin, a decrease in noise was detected after 15 minutes.

"In conjunction with cell imaging and post-experiment counting of colony-forming units, these results provide evidence that cell death can be sensed through measurements of cell-generated frequency noise, potentially providing a basis for rapid AST," Johnson and colleagues report.

Next steps include testing the new technique out on more antibiotics and bacteria. E. coli was kind of low-hanging fruit because of its relatively quick response to antibiotics. Such quickness is not always the case. Still, as Physics World reports, the group has already been awarded a patent for the method.