To examine why some fluoroquinolones are stronger than others, the researchers used X-ray crystallography to generate three-dimensional models of the interaction between TB’s DNA gyrase and five different versions of the antibiotic. Using this method, the researchers were able to see that the drugs are able to interact with the TB bacterial proteins at two different sites.
The discovery may help explain why fluoroquinolones are less effective against TB than against other bacterial infections but it also may help scientists develop fluoroquinolone derivatives that are stronger and more effective against TB.
“All together, these studies provide a wealth of information that drug companies can use to continue the development of fluoroquinolones,” said James Berger, PhD, professor of biophysics and biophysical chemistry at Johns Hopkins. “They hold a lot of promise for fighting drug resistance in bacteria that cause TB and many other diseases.”
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