Imaging probe breakthrough detects bacterial infections with high sensitivity

A new family of contrast agents developed by Georgia Tech researchers, called maltodextrin-based imaging probes, sneak into bacteria disguised as glucose food to detect bacterial infections in animals with high sensitivity and specificity.

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A new family of contrast agents developed by Georgia Tech (Atlanta, GA) researchers, called maltodextrin-based imaging probes, sneak into bacteria disguised as glucose food to detect bacterial infections in animals with high sensitivity and specificity. These agents can also distinguish a bacterial infection from other inflammatory conditions.

"These contrast agents fill the need for probes that can accurately image small numbers of bacteria in-vivo and distinguish infections from other pathologies like cancer," says Niren Murthy, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. "These probes could ultimately improve the diagnosis and treatment of bacterial infections, which remains a major challenge in medicine." Also, the maltodextrin-based imaging probes target a bacterial ingestion pathway, which allows the contrast agent to reach a high concentration within bacteria, says Murthy.

Described in an advance online edition of Nature Materials, the maltodextrin-based imaging probes consist of a fluorescent dye linked to maltohexaose, which is a major source of glucose for bacteria. The probes deliver the contrast agent into bacteria through the organism's maltodextrin transporter, which only exists in bacterial cells and not mammalian cells.

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A chemical design of the maltodextrin-based imaging probes, which are composed of maltohexaose conjugated to a fluorescent dye and are internalized by bacteria through the maltodextrin transport pathway. (Image courtesy of Niren Murthy)

In experiments using a rat model, the researchers found that the contrast agent accumulated in bacteria-infected tissues, but was efficiently cleared from uninfected tissues. They saw a 42-fold increase in fluorescence intensity between bacterial infected and uninfected tissues. However, the contrast agent did not accumulate in the healthy bacterial microflora located in the intestines. Because systemically administered glucose molecules cannot access the interior of the intestines, the bacteria located there never came into contact with the probe.

They also found that the probes could detect as few as one million viable bacteria cells. Current contrast agents for imaging bacteria require at least 100 million bacteria, explain the researchers.

In another experiment, the researchers found that the maltodextrin-based probes could distinguish between bacterial infections and inflammation with high specificity. Tissues infected with E. coli bacteria exhibited a 17-fold increase in fluorescence intensity when compared with inflamed tissues that were not infected.

Additional laboratory experiments showed that the probes could deliver large quantities of imaging probes to gram-positive and gram-negative bacteria for internalization. Both types of bacteria internalized the maltodextrin-based probes at a rate three orders of magnitude faster than mammalian cells.

"Maltodextrin-based probes show promise for imaging infections in a wide range of tissues, with an ability to detect bacteria in-vivo with a sensitivity two orders of magnitude higher than previously reported," says Murthy.

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Posted by Lee Mather

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