Gender-Specific Signatures Found in Gonorrhea Infection & Resistance Genes

Cases of the second most common notifiable disease in the United States, gonorrhea, have not only been on the rise but the bacteria that causes the disease, Neisseria gonorrhoeae, have also progressively developed resistance to most of the antibiotics currently available to fight the infection.

Now, a new study funded by the National Institutes of Health and led by researchers from Tufts University School of Medicine has identified gender-specific signatures in gonorrhea infection as well as resistant genes.

“We built on our earlier work on gene expression during infection in females to include both genders in the present analysis, so we see for the first time the expression profiles during active disease in males and their asymptomatic partners,” Caroline A. Genco, PhD, Arthur E. Spiller professor and chair of the department of Immunology at Tufts, said in a recent statement.

It is estimated that on an annual basis, a staggering 78 million individuals are infected with gonorrhea worldwide. While men tend to present with telltale symptoms—burning sensation when urinating, discharge from the penis, painful or swollen testicles—women, for the most part, tend to be asymptomatic. For both sexes, infection normally clears with treatment.

In an effort to better understand how the disease manifests in both genders, the researchers conducted the first full comparison of gonococcal gene expression and regulation in men and women infected with the sexually transmitted infection (STI) who were attending a clinic located in a country with high rates of gonorrhea and antibiotic resistance.

The team collected specimens from men who were attending the clinic for gonorrhea treatment and female partners who were going to the clinic to receive treatment after their partner had received a confirmed diagnosis of gonorrhea. Using RNA-sequencing, they were able to detect what host and bacterial genes were expressed during mucosal infection.

“We found that when the bacteria are infecting the male, it’s a different gene expression profile compared to when they are infecting the female,” Dr. Genco said.

The team found that in men specifically, 9% of gonococcal genes had increased expression; these genes were noted to have involvement in host immune cell interactions. Furthermore, 4% of genes were found to have increased expression specifically in women; these included phage-associated genes.

“When you consider how fundamentally different the 2 host environments are, this makes sense,” Dr. Genco added.

Using whole-genome sequencing, the research team found that both sexes presented antibiotic-resistant genotypes that were considered to be similar; however, these genes were expressed higher in men by fourfold compared with their female counterparts.

The sample size used for the study was small and potential variance in stages of infections in the male participants compared with the female participants were noted to be among the study’s limitations. In an effort to address these limitations, researchers are currently in the process of conducting a study where researchers will conduct additional genetic analysis on a larger scale.

With gonorrhea increasingly gaining resistance against available drugs, and cases of “super gonorrhea” being reported, more information is needed to better understand the infection; understanding how the bacteria manifests differently according to gender just supplies another piece to the puzzle that is the disease.