A scientific quest that started in 1905 has been achieved by scientists at McGovern Medical School, who reported that they are the first to grow a long-lasting tissue culture of the bacterium responsible for syphilis. Findings appeared in the journal mBio.
“This is a major advance in syphilis research,” said Steven Norris, Ph.D., the paper’s senior author and a professor of pathology and laboratory medicine. “It is one of the few major human bacterial pathogens that had not been cultured in vitro previously.”
Until now, researchers have had to study the bacterium named Treponema pallidum in animal models. Now, investigators can study the bacterium in long-lasting tissue cultures under laboratory conditions.
Syphilis is a sexually transmitted disease and affects as many as 56 million individuals worldwide, the authors report. It is typically treated with penicillin.
At the time of publication, the culture remained infectious and had been growing continuously for about eight months. “A long-term culture system could bolster genetic, pathologic and immunologic research of T. pallidum, as well as allow for the culture of related pathogenic species,” said Norris, who is a vice chair for research and the Robert Greer Professor in the Biomedical Sciences.
T. pallidum has been an elusive target of research, in part, because of its natural habitat. “The organism never touches the ground,” Norris said. “It’s only found in humans. It’s not found anywhere else in nature.”
In the past, if researchers wanted to study the pathogen, they injected animals with bacteria from a human host and had to wait a few weeks to confirm an infection. “It was a very inefficient process,” says Norris, who has been studying T. pallidum for more than four decades.
Norris and his collaborators designed the new system to mimic the environment where the bacteria are naturally found. “We thought that by creating tissue-like conditions, we’d be able to grow T. pallidum continuously,” he said. They designed a co-incubation system in which the spirochetes are grown with animal epithelial cells and fed periodically with fresh nutrients.
In order to preserve a near-homeostatic state, the researchers transfer the infected cells to a new culture medium about once a week. This approach is a modified version of a co-incubation system, first introduced in 1981 by researchers A. Howard Fieldsteel, Ph.D., David Cox, Ph.D., and Randolph Moeckli, that successfully kept the bacteria alive for about 18 days. The system described in mBio uses a more complex culture medium – one often used to culture the bacteria that cause Lyme disease, Norris said.
Diane Edmondson, Ph.D., the lead author and an assistant professor of pathology and laboratory, said accumulated knowledge about the life history of the organism has helped researchers recognize that T. pallidum does not grow like other organisms. “We expected they would grow a little faster than they do,” she said, “but maybe they’re just slow-growing organisms. One of the reasons for success is accepting that we’re never going to get very high-density cultures. We work with what it really is.”
Bo Hu, Ph.D., assistant professor of microbiology and molecular genetics, also assisted in the research by using a method called electron microscopy to show that the structure of the bacterium remains unchanged during culture.
The Centers for Disease Control and Prevention launched a syphilis eradication effort in 1998, but by 2017, infection rates in the United States had climbed to their highest levels since before the eradication program began.
Norris said he ultimately hopes to modify the system to make it more efficient by eliminating the need for tissue cells altogether. A simplified process might make it easier to develop new ways to detect, treat or prevent the infection, he says.
The new process for growing T. pallidum may also be used to culture spirochetes that cause syphilis-related diseases including yaws and bejel, the authors said, and they hope other groups adopt and use the method to grow and study the pathogens.
The study, titled “Long-term in vitro culture of the syphilis spirochete, Treponema pallidum subsp. pallidum,” was supported in part by National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R21AI128494). Norris is on the faculty of The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences.
– Adapted from a news release from the American Society of Microbiology.