Unweaving the Web of Bacteria's Antibiotic Resistance

A special technique allowed researchers to detail the structure of an enzyme that causes antibiotic resistance.

Researchers have begun to untangle antibiotic resistance through the first detailed biochemical characterization of a flavoenzyme involved in this resistance.

The antibiotic rifampicin (Rifampin), which treats tuberculosis, leprosy, and Legionnaire’s disease, is becoming less effective as the bacteria begins to build up a resistance. One of the mechanisms that leads to rifampicin resistance is the action of the enzyme Rifampin monooxygenase.

In a new study published in the Journal of Biological Chemistry and PLOS One, researchers used a special technique to describe the structure of this enzyme.

Antibiotic resistance is one of the major problems in modern medicine,” said researcher Heba Adbelwahab, first study author of the PLOS One paper. “Our studies have shown how this enzyme deactivates rifampicin. We now have a blueprint to inhibit this enzyme and prevent antibiotic resistance.”

Rifampin has been used for more than 40 years to treat bacterial infections, and was designed to prevent the bacteria from making RNA that is critical for growth.

For the study, researchers used a special technique called X-ray crystallography to describe the structure of the flavoenzyme, Rifampin monooxygenase. Additionally, researchers were able to report the biochemical studies that allows them to determine the mechanisms by which the enzyme deactivates the antibiotic.

“In collaboration with Professor Jack Tanner at the University of Missouri and his postdoc, Dr Li-Kai Liu, we have solved the structure of the enzyme bound to the antibiotic,” said lead researcher Pablo Sobrado. “The work by Heba, a visiting graduate student from Egypt, has provided detailed information about the mechanism of action and about the family of enzymes that this enzyme belongs to. This is all-important for drug design.”

The authors noted that the study’s findings represent the first detailed biochemical characterization of a flavoenzyme involved in antibiotic resistance.