Researchers discovered a molecule called pSma1 in oral bacterial cell samples from people with severe UC. This new mouth bacteria may be a potential disease progression marker, or a therapeutic target for UC, the investigators said.
The study, “Analysis of complete Campylobacter concisus genomes identifies genomospecies features, secretion systems and novel plasmids and their association with severe ulcerative colitis,” was published in the journal Microbial Genomics.
IBD is a chronic condition of the gastrointestinal tract, with UC and Crohn’s disease being the two major forms of the disease.
Crohn’s disease is characterized by the chronic inflammation of any part of the gastrointestinal (GI) tract, while UC involves the rectum and the large intestine (colon). In severe IBD cases, inflammation can spread further, and in some people who fail to respond to medicine, intestinal surgery may be required.
Campylobacter concisus is a type of bacteria that generally colonize the mouth cavity in healthy people. But it also has been associated with IBD and other diseases in the gastrointestinal tract.
“Oral bacteria enter the digestive system every day when we swallow food or saliva,” Li Zhang, PhD, the study’s senior study, said in a press release.
“Most of the bacteria are killed by acids in the stomach, but some can survive and colonize in the intestines,” Zhang said.
Until now, only three complete C. concisus genomes have been analyzed; however, none of them have been linked to UC. Further, C. concisus genomes from healthy individuals have not been investigated, limiting a comparison to identify strains associated explicitly with UC or Crohn’s disease.
To address this gap, an investigation of these strains of mouth bacteria was conducted by researchers based at the University of New South Wales (UNSW), in Australia. The team successfully analyzed the complete genomes of 13 C. concisus strains isolated mostly from the oral cavity of patients with UC and Crohn’s disease, and from healthy controls.
A comparison of these 13 strains, along with the three strains identified previously (available in public databases), found half — eight out of 16 — contained plasmids. Plasmids are small, circular DNA molecules inside bacterial cells that can carry genes encoding for proteins that may contribute to the severity of the bacterial infection (virulence). Plasmid DNA also can be shared between different bacteria species.
“A plasmid is outside the bacteria’s chromosomal DNA,” said Fang Liu, PhD, postdoctoral researcher at UNSW Science and study lead author.
“It’s considered a mobile genetic element, which means it can be transferred between different strains of the bacterium or even different species,” Liu said. “If the plasmid carries any virulence genes, the bacteria could gain that virulence.”
Of the six plasmids analyzed, two had an almost identical DNA sequence and were thus considered one plasmid. Also, two plasmids called pSma1 and pSma2 were found in one bacterial strain.
Further analysis found the numbers of pSma1 and pSma2 plasmids within each bacteria was between 60 and 70, whereas the remaining plasmids also had multiple copies but not as many. The pSma1 plasmid encoded two unknown proteins, while the pSma2 plasmid only encoded one unknown protein.
The potential association for each of the six plasmids with disease was examined by assessing their prevalence in 239 C. concisus strains in public databases in patients with different gastrointestinal disorders as well as in healthy controls.
The pSma1 plasmid was found in one strain from one individual with active Crohn’s disease, in one strain from an active UC patient, and in 12 strains from four UC patients who had undergone colon surgery due to disease severity. The pSma1 plasmid was not found in patients with diarrhea.
The prevalence of pSma1 in UC patients who had surgery was 27%, which was significantly higher than that in those with Crohn’s disease (3%), diarrhea (0%), and healthy individuals (5 %). Of the C. concisus strains isolated from these patients, 30% were positive for pSma1, which was significantly higher compared with strains isolated from patients with Crohn’s disease (2%), diarrhea (0%), and healthy controls (3%).
The prevalence of this plasmid, isolated from all patients with UC, also was significantly higher than in healthy people (controls) — 21% vs. 3%. The other plasmids did not show associations with disease.
Additional analyses confirmed that each bacteria cell contained more than 60 copies of the pSma1 plasmid. High numbers of plasmids may enhance a bacteria’s virulence.
“pSma1 is a very small plasmid,” said Liu. “It only has two genes, but it also has a high copy of 60, which means that one bacterial cell will contain 60 copies of this small plasmid.”
That could exacerbate its strength.
“The proteins encoded by this plasmid might be a virulence factor,” Liu added.
An examination of the DNA sequences from seven strains isolated from UC patients formed one cluster, regardless of the isolated strain’s geographical origin, suggesting that they are “phylogenetically close,” the researchers wrote. Of note, phylogenetics refers to evolutionary relationships between a species or group of organisms.
Finally, the complete genome of a C. concisus strain isolated from an intestinal biopsy of a patient with UC with the same oral strain isolated from that individual was almost identical.
“The finding that [pSma1] is associated with severe UC is particularly interesting, suggesting that future studies should be conducted to investigate whether [pSma1] is a disease progression marker and a therapeutic target for UC,” the researchers wrote.
“We may have found an area for future drug development for the prevention of severe ulcerative colitis,” said Zhang.” If we find out the plasmid plays a role in the pathogenesis, it could be quite easy to translate this finding into clinical use.”
“Treatments targeting the oral cavity could help reduce the load of the bacteria. We may not be able to eradicate this bacterium, but we could certainly reduce the load,” she added.