A new contrast agent that targets microbes can be used to illuminate bacterial infections in living animals. It could ultimately enable doctors to safely spare more of a limb during amputations.
It’s usually clear when a patient has a bacterial infection and needs to be treated with antibiotics, says Jason Bowling, director of epidemiology at the University of Texas Health Science Center at San Antonio, who was not involved with developing the imaging agent. But sometimes an infection is more difficult to diagnose. For example, it can be difficult to tell when a patient who has pain at the site of a hip or knee replacement has an infection. This sometimes leads doctors to prescribe antibiotics when they aren’t necessary.
An imaging scan capable of detecting bacteria would quickly answer the question, sparing uninfected patients from unnecessary antibiotics or even from surgery to remove the implant. Where there is an infection and the implant is removed, imaging could help ensure that no new hardware is implanted until the infection has been completely cleared.
It’s challenging to image infections because many of the molecules used to target bacteria can accumulate in tissue that is merely inflamed rather than infected, says Niren Murthy, professor of biomedical engineering at Georgia Tech, who was involved with developing the new agent. The new imaging agent is taken up by bacteria in large quantities, but it won’t stick around in other tissue. “We had to find something very specific to bacteria,” he says.
Murthy’s group stole a trick from a group of viruses that gets its genome inside bacteria by attaching it to a bacterial food source, a carbohydrate called maltohexaose. Bacteria have proteins on their cell walls whose job is to bring maltohexaose inside the cell, and this happens even if that maltohexaose is attached to an imaging agent. Animal cells don’t have these proteins, so they don’t take up the contrast agent.
There are already two bacterial imaging agents on the market for use in preclinical research. But these are not as sensitive or as versatile as the Georgia Tech probe, says W. Matthew Leevy, professor of chemistry and director of biological imaging research at the University of Notre Dame. Those earlier imaging agents work by a different mechanism—they stick to bacterial cell walls rather than accumulate inside the cell. The Georgia Tech probe is two orders of magnitude more sensitive than any made in the past, which means it can detect much smaller populations of bacteria. Leevy says it should be compatible with a wide array of imaging technologies, including MRI, PET, and fluorescence imaging.
In a paper published online in the journal Nature Materials this week, Murthy describes imaging bacterial infections in living mice using the new contrast agent—maltohexaose attached to a fluorescent protein. Fluorescent imaging is useful for animal studies, but the method can’t be used to visualize the deep tissues of the body because the light simply cannot get out. Murthy is now coupling maltohexaose with imaging agents suitable for imaging with PET.
It will be critical to make the new contrast agent compatible with imaging technologies commonly found in hospitals, says Bowling, who runs a clinic where he monitors patients with bone infections. He says it’s often difficult to decide whether a patient has recovered and can be taken off the drugs. “There’s not a lot of data on when to stop treatment, and you can’t tell if you’ve truly cleared an infection or not,” he says. Other uses for the imaging agent might include helping doctors determine whether a diabetic’s foot problems are due to infection, and visualizing the extent of an infection in patients who need an amputation.
Leevy says he expects the agent to be available to researchers soon, but he says it could be difficult to bring the imaging technology into the clinic. While it could make a big difference for some patients, he says, the narrow potential market could discourage a company from making the large investment necessary to bring the agent through clinical trials.
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