Nature Chemical Biology paper suggests that bacteria detect the antibiotic itself and not its effect on the bacterial cell wall.

Researchers report that they have figured out how bacteria recognize and develop resistance to vancomycin. Details were published online April 11 in Nature Chemical Biology, and the paper is titled “A vancomycin photoprobe identifies the histidine kinase VanSsc as a vancomycin receptor.”

The study was conducted by Gerry Wright, Ph.D., a professor in the department of biochemistry and biomedical sciences at McMaster University in collaboration with colleagues at the John Innes Centre in Norwich and the University of Cambridge in the U.K.

“For years it was thought that resistance would be slow to emerge since vancomycin works in an unusual way,” remarks Dr. Wright. “But with the widespread use of the drug to treat infections caused by the hospital superbug MRSA, it has become a serious clinical problem.”

Vancomycin is used to treat enterococcal infections that develop in patients following abdominal surgery. Enterococcal bacteria first developed resistance to vancomycin in 1986, and the first case of vancomycin-resistant MRSA was reported in 2002.

Scientists have long debated over whether bacteria sense the drug itself to trigger resistance or whether they sense the impact it has on the cell wall of bacteria. Most antibiotics work by inhibiting an enzyme, but vancomycin binds to cell wall building blocks, causing a weakness in the structure of the cell wall so that the cell bursts and dies.

Dr. Wright’s group studied the vancomycin-resistance mechanism in the harmless soil bacteria Streptomyces coelicolor. They showed that bacteria detect vancomycin itself. Additionally, their preliminary experiments suggest that the same mechanism exists in disease-causing bacteria.

“We have finally cracked the alarm system used by bacteria, and hopefully new antibiotics can be developed that don’t set it off,” says Mark Buttner, a study collaborator and senior scientist at the John Innes Centre.

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