Fluorescence-based drug: A ray of hope in fighting antibiotic resistance

Chinese scientists have developed a simple and fast assay system based on a fluorescent probe and optical detection that can detect the activity of multidrug-resistant (MDR) pathogens. 

Carbapenems are like cephalosporins and penicillins and belong to the class of beta-lactam antibiotics. Although some bacterial strains have found powerful strategies to resist beta-lactam antibiotics by producing a class of cleaving enzymes, the beta-lactamases, most beta-lactamases cannot affect the carbapenems.

Carbapenems are also called "antibiotics of last resort" and can fight infections for which other drugs have long lost their effectiveness.Therefore, these substances, are the drug of choice for several diseases such as urinary-tract and abdominal infections as well as hospital-acquired pneumonia, if they are caused by multidrug-resistant bacteria. 

However, over the last decades some pathogenic strains have emerged over that hold up the ability to resist carbapenems. To find out whether a pathogen contains carbapenem-cleaving enzymes, the carbapenemases, Hexin Xie at East China University of Science and Technology and his team have set up a strategy to identify those pathogens that carry the carbapenemases.

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The researchers have created a molecule that has the similar structure as the carbapenems but has a fluorogenic dye attached.

If this carbapenem-mimicking compound, CVB-1, is recognized by a carbapenemase, for example, in an bacteria extract, CVB-1 is cleaved and undergoes spontaneous degradation. As this destroys the electronic interaction of the attached dye with the carbapenem compound, the dye turns into a green fluorescent molecule, which means, if it is irradiated with light of a certain wavelength, it emits intense green light. 

Thus, the assay in principle works as follows: If there is an active carbapenemase present, for example, in a bacteria extract, a couple of minutes later the sample glows green upon excitation. Xie and his colleagues said: "CVB-1 <...> is essentially non-fluorescent <...>, and the addition of triggers the turn-on of the fluorescent signal upon excitation <...> with over 200-fold enhancement ratio."

This fluorescence allows the detection of antibiotic resistance activity. Thus, this fluorescence-based assay system, it would be possible to diagose the presence of carbapenem-resistant bacteria (such as certain Enterobacteriaceae and Klebsiella pneumoniae strains) during an infection.

Using this system, an overuse of non-effective drugs could be avoided and more specific treatment strategies could be designed. The scientists have performed several tests to prove that their CVB-1 assay is specific, that the detection limit is low, and that it can indeed be used in live systems.

This incredible approach have been introduced in the journal Angewandte Chemie.