Scientists can now find bacteria by listening for their gas

(Written as part of my application to MIT's Science Journalism Master's Program in 2019)

When asked to find an object, many of us rely on only one of our senses: sight. But what if the best way to find something was to listen? Many techniques in science and medicine are similarly biased towards sight (think of all the different types of microscopes), but scientists at the California Institute of Technology had an idea of using sound to tag bacterial cells in the body. With acoustic tags we can echolocate the tagged bacteria deep inside our bodies. Knowing the location of naturally occurring bacteria in the body can give us invaluable insight as to their role in our health. We could even use engineered bacteria to release drugs to a specific area by tracking their location in the body.

To develop these acoustic tags, Shapiro and colleagues borrowed a trick from aquatic bacteria that produce tiny bubbles called gas vesicles. In nature, these gas bubbles help water-dwelling bacteria float. By engineering gut bacteria to produce gas vesicles, the researchers acoustically tracked their movement using an ultrasound.

Ultrasound is, of course, not a new idea. Doctors use it to watch babies develop in the womb, look at internal organs, and to identify tumors. The technique remains a valuable tool in medicine in that it is sensitive and noninvasive. The ultrasound machine works by sending inaudible sound waves through the body and recording the waves that bounce back to the detector. Different types of tissue echo sound waves in different ways and by collecting the various echoes at several positions, you can create a picture of the underlying tissue. Shapiro and colleagues took advantage of the simple fact that sound travels through liquid differently than through gas to locate their tagged bacterial cells within the guts of mice.

Our guts are an ecosystem of bacteria. From birth we are colonized by microbes that help us digest and extract nutrients from food, fight off harmful bacteria and even regulate brain health. It’s tough to untangle the complex interactions between our bodies and the microbes living deep in our organs if we can’t even see them. Pinpointing the location of microbes using sound waves could help solve this major challenge in medicine. Knowing where in the body particular microbes reside gives us insight into the potential function and impact these microbes have on our health.

Besides acoustic tags there are two main ways to study the bacteria in our innards, and both have significant limitations. Bacteria can be labeled radioactively and visualized on x-rays but repeated, prolonged exposure to radioactivity and x-rays can severely damage our bodies. Bacteria can also be tagged with bioluminescent molecules that glow when excited with light from a high-power microscope. While these luminescent tags are used widely throughout science and medicine, the molecules can only be seen in a living organism reliably if they’re close to the surface of the body and even then, the signal is fuzzy.

For example, with bioluminescent tags the researchers were only able to vaguely see that the tagged gut bacteria were in the abdomen, whereas the location of the same bacteria but with an acoustic tag was mapped to the colon.

Excerpt of Figure 1 from source article showing TEM images of bacterial cells expressing the luminescent gas bubbles (top row) and the reporter bubbles themselves (bottom row).

With a microbiome census of your gut your doctor could easily locate and track the bacteria present in a precise location within your gastrointestinal tract and use this information to study your unique microbiome and the impact different families of bacteria have on your health.

The potential of engineered bacteria is particular exciting. Scientists have been using bacteria as cellular factories for decades because of the ease in introducing new DNA. With this technology bacteria can be targeted to specific areas in the body to release molecules only in the affected area. This is especially useful in treating cancer where the targeted delivery of antitumor drugs directly to the tumor could make all the difference in eradicating cancerous cells without causing adverse side effects on your healthy cells. These drugs can even be tailored specifically to the patient by altering the compound or molecule the bacteria are programmed to produce.

Instead of relying on synthesized chemical compounds to treat illness, in the future doctors might prescribe yogurt filled with an army of bacteria equipped to home in and administer drugs from within your own body. The ability to precisely locate these bacteria-turned-factories within the body could be a significant factor in treating patients in the future.

Using ultrasound to find bacteria is like a game of microbial Marco Polo. Finding a specific type of bacterial cell amidst a teeming troop of trillions of cells is hard, but by engineering cells with a voice we can hear them when they yell “Polo!”

Source article: Shapiro, M.G. et al. “Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts.” Nature letters. 2018.