Steadily and relentlessly, the bacterium that causes gonorrhea has slipped past medicine’s defenses, acquiring resistance to once-reliable drugs, including penicillin, tetracycline and ciprofloxacin. These former stalwarts are no longer used to treat the sexually transmitted disease.

Neisseria gonorrhoeae/CDC

In 2010, after some strains of Neisseria gonorrhoeae, the bacterium responsible for gonorrhea, began showing resistance to one of the last remaining classes of antibiotics, the Centers for Disease Control and Prevention began recommending “dual therapy,” meaning that doctors now prescribe two drugs at the same time to fight gonorrhea. Currently, those two drugs are ceftriaxone, a member of the cephalosporin class of antibiotics, and azithromycin.

With fears increasing that gonorrhea could breach these last defenses, the work of researchers like crystallographer Christopher Davies, Ph.D., is crucial.

“We’re looking at a molecular level at the events that have got everybody worried out there in the clinics,” said Davies, a professor in the Department of Biochemistry & Molecular Biology and director of the MUSC Center for Structural Biology.

Davies’ team has just published a paper showing how cephalosporins bind and inactivate a gonococcal protein dubbed penicillin-binding protein 2 (PBP2). Led by postdoctoral fellow Avinash Singh, Ph.D., the researchers showed the protein undergoes key structural changes, including twisting and rolling of a loop to bind the antibiotic, that enhance the reaction with cephalosporins. Without these changes, the protein would react much more slowly with the antibiotic.

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