A research team led by scientists at the University of Texas at Austin has developed chemical “probes” to help identify an enzyme produced by certain types of E. coli and Streptococcus pneumoniae that is known to break down several common types of antibiotics, making the bacteria dangerous resistant to treatment.
“In response to antibiotic treatment, bacteria have evolved various mechanisms to resist that treatment, and one of those mechanisms is to make enzymes that basically ‘chew up’ the antibiotic before it can do its job,” said Emily Que, an associate professor of chemistry at the University of Texas at Austin and one of the team’s lead researchers.
The tool we developed gives us critical information that can keep us one step ahead of the deadly bacteria.”
In a paper published online May 26 in the Journal of the American Chemical Society, researchers focused on the threat posed by a bacterial enzyme called New Delhi metal-beta-lactamase (NDM).
They set out to create a molecule that glows when it comes in contact with the NDM enzyme.
When these chemical “probes” are added to a test tube, they bind to enzymes and glow.
Such tools could be used to alert doctors to what bacterial threats are affecting their patients and to tell them which antibiotics to use.
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NDM breaks down antibiotics such as penicillin, cephalosporins and carbapenems, which are some of the safest and most effective treatments for bacterial infections.
Other classes of antibiotics also exist, but they may have more side effects, have more drug interactions, and may not be as readily available in some parts of the world.
In addition to showing the presence of the NDM enzyme, fluorescence chemistry “probes” developed by Que and Walt Fast (Professor of Chemical Biology and Pharmaceutical Chemistry) may help to find a different approach to combat these resistant bacteria.
One treatment that doctors use against resistant bacteria is a combination of a common antibiotic and an inhibitor.
Although there are currently no known clinically effective inhibitors against NDM producing bacteria, Que’s probe can help find one.
Once the probe binds to the enzyme and starts to glow, if an effective inhibitor is introduced, it will loosen the “probe” and the glow will stop.
This allows scientists to test a large number of potential drugs very quickly — a research that Que and FAST hope to continue in the future.
“This allows us to work towards developing treatments and ultimately to understand the evolutionary characteristics of this protein,” said Radhika Mehta, a PhD graduate student at the University of Texas at Austin and lead author of the paper.
Mehta is currently a postdoctoral fellow in the Mawson Lab at the University of California, Berkeley.
The study also looked at a process called vegetative immunity, which comes from the production of proteins in the body in response to infection.
These proteins rob the body of all available metals, such as zinc, needed to make NDM, making the bacteria more vulnerable.
“The evolution of this bacterium since it was discovered in 2008 suggests that it is not only developing antibiotic resistance, but also trying to fight this natural human immune process.
It was particularly scary, “Que said.
The “probe” developed by Que can also be used to study nutritional immunity and NDM because it only glow-up when the zinc needed to form enzymes is present.