Engineered bacteria reflect ‘sonar’ signals for ultrasound imaging

Technology News | January 9, 2018

By Rich Pell

Medical Electronics Materials & processes Data Acquisition Analog Sensing / Conditioning Wireless Communications

Similar to how submarines reflect sonar to reveal their locations, such engineered bacterial cells promise the ability to be injected therapeutically into a patient’s body — e.g., as probiotics to help treat diseases of the gut or as targeted tumor treatments — and then located with the use of ultrasound machines, which generate images that reveal the locations of the microbes. The images would let doctors know if the treatments made it to the right place in the body and were working properly.

“We are engineering the bacterial cells so they can bounce sound waves back to us and let us know their location the way a ship or submarine scatters sonar when another ship is looking for it,” says Mikhail Shapiro, assistant professor of chemical engineering, Schlinger Scholar, and Heritage Medical Research Institute Investigator. “We want to be able to ask the bacteria, ‘Where are you and how are you doing?’ The first step is to learn to visualize and locate the cells, and the next step is to communicate with them.”

Currently, visualizing bacterial cells as well as communicating with them — i.e., gathering information on what’s happening in the body and giving the bacteria instructions about what to do next — is not yet possible. Imaging techniques that rely on light — such as taking pictures of cells tagged with a “reporter gene” that codes for green fluorescent protein — only work in tissue samples removed from the body, as light can’t penetrate into deeper tissues of the body, like the gut, where the bacterial cells would reside.

Ultrasound techniques, however, can offer a solution because sound waves can travel deeper into bodies. Shapiro says the idea occurred to him when he learned about gas-filled protein structures in water-dwelling bacteria that help regulate the organisms’ buoyancy.

The structures – called gas vesicles – could, he hypothesized, bounce back sound waves in ways that make them distinguishable from other types of cells. Since then, the researchers have demonstrated that the gas vesicles can indeed be imaged with ultrasound in the guts and other tissues of mice.

The next step was to transfer the genes for making gas vesicles from the water-dwelling bacteria into a different type of bacteria. The researchers chose Escherichia coli (E. coli) – a bacteria commonly used in microbial therapeutics, such as probiotics.

“We wanted to teach the E. coli bacteria to make the gas vesicles themselves,” says Shapiro. “I’ve been wanting to do this ever since we realized the potential of gas vesicles, but we hit some roadblocks along the way. When we finally got the system to work, we were ecstatic.”

Ultimately, the solution involved transferring a mix of gas-vesicle genes from two different water-dwelling bacteria. Some of the gas vesicle genes code for proteins that act as building blocks of the vesicles themselves while others help in actually assembling the structures. Subsequent experiments demonstrated that the engineered E. coli could indeed be imaged and located within the guts of mice using ultrasound.

“This is the first acoustic reporter gene for use in ultrasound imaging,” says Shapiro. “We hope it will ultimately do for ultrasound what green fluorescent protein has done for light-based imaging techniques, which is to really revolutionize the imaging of cells in ways there were not possible before.”

The technology should be available soon to scientists who do research in animals, say the researchers, while developing the method for use in humans will likely take many more years. For more, see “Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts.”