Northwestern Medicine scientists have identified a novel mechanism utilized by the bacteria responsible for gonorrhea to evade immune detection and achieve widespread infection, according to a recent study published in the Proceedings of the National Academy of Sciences.
Neisseria gonorrhoeae causes gonorrhea, which one of the most common sexually transmitted infections; if not treated promptly with antibiotics, the disease can cause infertility, sepsis and pregnancy complications.
The N. gonorrhoeae gene PilE codes for the PilE protein, a subunit of the type IV pilus, a hairlike structure found on the bacteria’s surface. The expression of PilE protein variants occurs through the process of pilin antigenic variation, which allows the bacteria to evade the immune system and infect healthy host cells.
“This system allows the bacterium to continually change the sequence of the pilin protein so that immune responses are not effective in recognizing this major antigen, pilin, and stopping reinfection,” said Hank Seifert, PhD, the John Edward Porter Professor of Biomedical Research and a professor of Microbiology-Immunology, who was senior author of the study.
Until now, however, the molecular mechanisms driving pilin antigenic variation have remained elusive, according to Seifert.
Using various approaches to study N. gonorrhoeae bacterial strains, the investigators discovered that two conserved restriction-modification systems cleave, or break apart, undermethylated DNA sequences (5′-CCGG sites) within a small subset of cells at the pilE gene and the silent pilS copies. They also found that this cleavage is an important process for pilin antigenic variation.
Simultaneously, they found that this cleavage reduced bacterial fitness, the bacteria’s ability to adapt and survive in certain environments, which suggests a “trade-off” between bacterial diversification and growth.
“On one hand, you increase adaptability and on the other you decrease the fitness,” said Selma Metaane, PharmD, PhD, a postdoctoral fellow in the Department of Microbiology-Immunology and lead author of the study.
The study uncovers a previously unknown role for restriction enzymes in driving antigenic variation in N. gonorrhoeae.
“This study is important because it shows that these two defense modules are there for another purpose: they’ve been co-opted to do antigenic variation as opposed to the standard role of protecting bacteria from invading bacteriophage viruses or other foreign DNA. So, it’s combining two well-established systems that were not known to be linked before,” Seifert said.
This work was supported by the National Institute of Allergy and Infectious Disease grants R37AI033493, R01AI146073 and R21AI148981.
