UVA Reveals How ‘Super Gonorrhea’ Resists the Human Immune System

Good news in the battle against the growing threat of drug-resistant “super gonorrhea”: Researchers at the University of Virginia School of Medicine and their collaborators in the United Kingdom have discovered a new way that the bacteria that cause gonorrhea resist the body’s immune defenses. Scientists can use this knowledge to develop vaccines or empower our immune system to take down a sexually transmitted bug that has already conquered most antibiotics.

“Every time we think we understand how gonorrhea bacteria manage to survive and cause disease in people, we learn something new,” said lead researcher Alison K. Criss of UVA’s Department of Microbiology, Immunology and Cancer Biology. “Our discovery is especially exciting because it opens up new ways to tackle the growing threat of untreatable gonorrhea.”

Alison Criss was a lead researcher on the new study, along with UVA biomedical sciences graduate student Stephanie Ragland and two collaborators in the U.K. (Photo by Dan Addison, University Communications)

Gonorrhea: Widespread and Dangerous

More than 78 million people contract gonorrhea each year, according to the World Health Organization, with more than 800,000 of those cases reported in the United States. The sexually transmitted disease has traditionally been treated with antibiotics, but the rise of drug-resistant gonorrhea has prompted the U.S. Centers for Disease Control to label it an “urgent threat.” The CDC estimates that 246,000 gonorrhea infections in the U.S. each year are resistant to at least one antibiotic. That’s an alarming figure, considering gonorrhea can lead to blindness, infertility and serious infections in the heart and nervous system, possibly even resulting in death.

UVA’s new research sheds important light on how the gonorrhea bacterium defeats the body’s antimicrobial defenses. Gonorrhea, the scientists determined, takes a two-fisted approach to neutralizing lysozyme, an enzyme that degrades bacteria and is abundant in tears, saliva and other secretions at body sites where the gonorrhea bacteria grows. Gonorrhea produces two proteins, known as inhibitors, that bind directly to lysozyme, preventing it from doing its job. Together, gonorrhea’s inhibitors “confer full resistance to this abundant antimicrobial defense,” the UVA researchers write in a new scientific paper.

When the researchers created a version of gonorrhea that lacked the two inhibitors, lysozyme killed the bacteria much more easily. Both of the inhibitors were found on the surface of the gonorrhea bacteria, making them able to be recognized by the immune system. That suggests that scientists could develop drugs or vaccines to make the bacteria susceptible to lysozyme, a major part of the body’s natural immune defense.

“It’s fascinating that the gonorrhea bacteria use two independent proteins to inhibit lysozyme, one of the main enzyme defenses our bodies have against bacteria,” said the study’s first author, Stephanie Ragland, a graduate student in the UVA biomedical sciences program. “Our finding suggests that lysozyme resistance is key to the survival of the gonorrhea bacterium. Going forward, we want to understand exactly how these lysozyme inhibitors work, and when and how the bacteria release them. This knowledge will help us develop new drugs or vaccines against gonorrhea, which are urgent priorities of the CDC and World Health Organization.”

Gonorrhea Findings Published

The researchers have published their findings in the scientific journal PLOS Pathogens. The research team consisted of Ragland and Criss, along with collaborators Marίa V. Humbert and Myron Christodoulides of the University of Southampton in the United Kingdom.

The work was supported by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases and the National Institute of Research; the Medical Research Council of the U.K.; and the UVA Robert R. Wagner Fellowship, awarded to Ragland.

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