Bacteria designed to reflect ultrasound give doctors new look into human body

Special bacteria have been created that reflect ‘sonar’ signals from ultrasound imaging, allowing doctors to see how drugs and treatments are moving around the body.

The ultimate goal is to be able to inject therapeutic bacteria into a patient’s body - for example, as probiotics to help treat diseases of the gut or as targeted tumour treatments - and then use ultrasound machines to hit the engineered bacteria with sound waves to generate images that reveal the locations of the microbes.

The pictures 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,” said assistant professor Mikhail Shapiro.

“We want to be able to ask the bacteria, ‘Where are you and how are you doing?’ The first step is to learn to visualise and locate the cells and the next step is to communicate with them.”

The idea of using bacteria as medicine is not new. Probiotics have been developed to treat conditions of the gut, such as irritable bowel disease, and some early studies have shown that bacteria can be used to target and destroy cancer cells.

Visualising these bacterial cells as well as communicating with them - both to gather intelligence on what’s happening in the body and give the bacteria instructions about what to do next - is not yet possible.

Shapiro wants to solve this problem with ultrasound techniques because sound waves can travel deeper into bodies.

He says he had a eureka moment about six years ago when he learned about gas-filled protein structures in water-dwelling bacteria that help regulate the organisms’ buoyancy.

Shapiro hypothesised that these structures, called gas vesicles, could bounce back sound waves in ways that make them distinguishable from other types of cells. Indeed, Shapiro and his colleagues demonstrated that the gas vesicles can be imaged with ultrasound in the guts and other tissues of mice.

The team’s next goal was to transfer the genes for making gas vesicles from the water-dwelling bacteria into a different type of bacteria - Escherichia coli (E. coli), which is commonly used in microbial therapeutics, such as probiotics.

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

One of the challenges the team hit involved the transfer of the genetic machinery for gas vesicles into E. coli. They experimented with several different types of bacteria until finally settling on a mix of genes from two species.

The gas vesicle genes code for proteins that act like either bricks or cranes in building the final vesicle structure; some of the proteins are the building blocks of the vesicles, while some help in actually assembling the structures.

Subsequent experiments from the team 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,” Shapiro said. “We hope it will ultimately do for ultrasound what green fluorescent protein has done for light-based imaging techniques, which is to really revolutionise the imaging of cells in ways there were not possible before.”

The researchers say the technology should be available soon to scientists who do research in animals, although it will take many more years to develop the method for use in humans.

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