disease-causing bacteria are gaining resistance to antibiotics by producing enzymes that deactivate them. A study has decoded the structure of the enzyme that helps bacteria gain resistance to a specific class of antibiotics.
This is crucial because this class of antibiotics was the only remaining lot so fat to be able to fight resistant bacteria. Experts say understanding the enzyme's structure will help design effective antibiotics.
When the antibiotic and the enzyme react, the enzyme works by modifying the antibiotic's active site. Active sites are specific points where the enzyme binds to the antibiotic.
Structural changes in the bacterial enzyme include a long helical loop that covers the active site. This results in the antibiotic not being able to bind itself to the bacterium. Thus, it does not function.The researchers said the modified structure indicated that the bacterium was becoming resistant to new antibiotics.
"Most antibiotics are natural products (or their derivatives) and so it was expected that naturally occurring enzymes would act on them. What is surprising is that some of these enzymes have mutated to also act on completely synthetic antibiotics," says Erick Strauss of Stellenbosch University, South Africa.
The authors suggest the structural changes themselves could be used against bacteria by making new antibiotics. "The results will help antibiotic drug development teams to carefully consider which drugs are most likely to be resisted and thus aid in developing dual strategies of antibiotic development--where one drug is the true antibiotic and the other targets the resistance-inducing enzyme," says Strauss.
The paper was published in the early online edition of the journal EMBO reports.
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