Finding new targets for attack on the bacterium that causes gonorrhea

April 9, 2014 § Leave a comment

Membrane vesicles from a strain of Neisseria gonorrhoeae visualized by transmission electron microscopy. Image provided by Aleksandra Sikora.

Membrane vesicles from a strain of Neisseria gonorrhoeae visualized by transmission electron microscopy. Image provided by Aleksandra Sikora.

April is Sexually Transmitted Disease Awareness Month and a good time to discuss Neisseria gonorrhoeae, the bacterium that causes gonorrhea. There aren’t any preventative vaccines for gonorrhea, and the bacterium is growing increasingly resistant to the antibiotics available to treat it. In a paper recently published in the journal Molecular & Cellular Proteomics, researchers describe exploring the exterior coat of the bacterium in hopes of finding new candidate proteins that might one day be targeted with drugs or used for the development of a vaccine.

Gonorrhea (colloquially called “the clap”) infects both men and women in the genitals, rectum and throat. In women, the infection can cause pelvic inflammatory disease, which can lead to tubal infertility, ectopic pregnancy, and chronic pelvic pain. According to the Centers for Disease Control and Prevention, gonorrhea is a very common infection, especially among people between 15 and 24 years old. The agency estimates there are 820,000 cases of gonorrhea every year in the U.S.

Aleksandra Sikora at Oregon State University and her team focused on the outermost membrane of Neisseria gonorrhoeae because that organelle is critical for the bacterium’s survival and pathogenesis. The envelope allows the bacterium to take up nutrients and “navigate the establishment of infection, host tissue destruction and suppression of host immune responses,” she explains.

The cell envelope occasionally pinches out in places to form membrane vesicles. These spheres contain proteins, lipopolysaccharides and various nucleic acids. “There are myriad processes that membrane vesicles are involved in, including biofilm formation, transfer of genetic material, delivery of virulence factors, antibiotic resistance, intra- and interspecies communication, and induction of an inflammatory response,” Sikora says.

Sikora and colleagues analyzed both the cell envelope and the membrane vesicles by a proteomic method that gives investigators a catalog of all the proteins present in those parts. The work was labor-intensive. Most of the proteins were not expressed in large quantities, which meant that the researchers had to make sure not to lose any during their experiments and had to concentrate a lot of cell envelopes and membrane vesicles to get enough material with which to work.  “In our protocol, spontaneously released membrane vesicles were harvested from one-liter volumes of Neisseria gonorrhoeae culture supernatants by filtration and ultracentrifugation procedures,” Sikora says. “Harvesting the membrane vesicles took about three days, and the entire procedure, from the start of the experiment to obtaining the final results, took usually seven days.”

In the end, the investigators discovered a protein in the cell envelope and membrane vesicles that is essential for the bacterium’s survival. They also found other proteins that appear to be important for the bacterium’s ability to counter antibiotics. “Together, these studies warrant further investigations of the newly identified proteins as potential targets for new therapeutic interventions,” Sikora says.

The investigators now are working on two different projects with the proteins they identified. They are evaluating them as vaccine candidates and targeting them with chemical probes to see if they can better understand the roles they play in the bacterium’s infection process and lifecycle.

Recordings of gonorrhea cases go back to biblical times. As Sikora points out, “This study shows that, despite many years of research in the Neisseria gonorrhoeae field, there is still much to learn about the agent of this ancient human disease.”

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