Editors' ChoiceInfectious Disease

Johnny, Johnny, Eating Sugar?

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Science Translational Medicine  10 Aug 2011:
Vol. 3, Issue 95, pp. 95ec129
DOI: 10.1126/scitranslmed.3003000

Just like Johnny in the nursery rhyme, bacteria love sugar. But unlike mammals, bacteria can also use maltohexaose as a source of glucose, which they take up using a bacteria-specific maltodextrin transport pathway. Maltohexaose may be a mere sugar, but thanks to new work by Ning et al., it may be the key to detecting early stages of bacterial infection.

Ning et al. have developed maltodextrin-based imaging probes (MDPs), consisting of fluorescent dyes conjugated to maltohexaose, that are rapidly taken up by bacteria via their maltodextrin transport pathway. These MDPs, when administered systemically to rats, can cross blood vessel walls and enter tissues. They do not, however, enter the gut lumen or outer layers of mammalian skin, which is advantageous because they do not label the normal bacterial microflora present in the gut and on the surface of the skin.

First, Ning et al. injected rat thigh muscles with Escherichia coli bacteria and then demonstrated that systemically administered MDPs could detect as few as 105 bacterial colony forming units (CFUs). This is a marked improvement over currently available probes such as zinc-dipicolylamine and antimicrobial peptides, which cannot detect fewer than 107 to 108 bacterial CFUs in vivo. Thus, MDPs have a sensitivity that is two orders of magnitude greater than that of existing probes for imaging bacteria.

Ning et al. go on to show that MDPs have a 1000-fold greater specificity for bacteria than they do for mammalian cells. In addition, MDPs can distinguish between active bacterial infections and inflammation caused by injection of lipopolysaccharides or inactive bacteria.

The specificity and sensitivity of MDPs suggests that they may be useful for detecting the earliest stages of bacterial infection in humans. However, their principal limitation at this point is that only fluorescent dyes have been attached to maltohexaose. Imaging deep tissues with fluorescent dyes in large mammals like us is not practical. It remains to be seen whether maltohexaose could be tagged instead with iodine (used in computed tomography), gadolinium (used in magnetic resonance imaging), or a radionuclide (like those used in nuclear scintigraphic scanning). Nevertheless, the work of Ning et al. suggests that MDPs deserve further investigation and, with further development, they may be useful for the clinical detection of early bacterial infections in humans. Perhaps in the future we will be able to open Johnny’s mouth and indeed see sugar, as the nursery rhyme says!

X. Ning et al., Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity. Nat. Mater. 10, 602–607 (2011). [Abstract]

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