A tummy invader: This bacterial molecule may be key to fighting stomach cancer
Researchers identify a novel way of how a common bacterium can learn to live within the human stomach
- Date:
- April 12, 2021
- Source:
- Osaka University
- Summary:
- Researchers found that H. pylori bacterial strains with low expression of a small RNA molecule called HPnc4160 are more likely to adapt to living in the human stomach. Gastric cancer patients have lower levels of HPnc4160, as well as higher levels of pathogenic bacterial proteins, than individuals without cancer. This work provides crucial knowledge for the development of new treatments for chronic H. pylori infections and gastric cancer.
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Humans are exposed to many types of bacteria daily, the majority of which are harmless. However, some bacteria are pathogenic, which means they can cause disease. An extremely common pathogenic bacterial infection is Helicobacter pylori (H. pylori) in the stomach, where it can lead to chronic inflammation (gastritis), ulcers, and even cancer. A group of researchers from Osaka University have determined a specific molecular mechanism that H. pylori uses to adapt to growing in the human stomach for long periods of time.
In a report published in Nature Communications, this group found that a small RNA molecule called HPnc4160 plays a key role in how H. pylori invades the stomach and leads to disease.
Previous studies showed that HPnc4160 is conserved in different strains of H. pylori, suggesting that it has an important function. Yet, the amount of this molecule produced in the bacteria is variable among strains. Genetic analysis revealed that a specific part of the H. pylori gene, called the T-repeat region, varied in length from strain to strain. The researchers became interested in how this region affected HPnc4160 expression. Additionally, they were curious how these fluctuations would allow some strains to colonize the human stomach more efficiently than others.
"Slight differences in the genetic sequence of H. pylori can sometimes give certain strains advantages over others that allow it to grow better," says lead author of the study Ryo Kinoshita-Daitoku. "We were interested in the genetic and molecular reasons behind why particular strains are more pathogenic and can live in the stomach for decades, leading to cancer development."
To address these questions, the researchers infected gerbils and mice with wild type (normal) H. pylori for 8 weeks, then extracted and genetically characterized the mutant strains that appeared. They discovered that strains with a higher number of T-repeats had lower expression of HPnc4160.
"We found that the H. pylori strains with low HPnc4160 levels were more infectious," explains Hitomi Mimuro, senior author. "When this RNA was completely absent, the amounts of several bacterial pathogenic factors significantly increased and the strain showed stronger colonization within the rodent stomach."
One of the pathogenic factors was the bacterial protein CagA, which is known as an oncoprotein because it can promote cancer development.
"Interestingly, we observed longer T-repeat regions, lower levels of HPnc4160, and higher levels of CagA in gastric cancer patients compared with those not suffering from cancer," describes Kinoshita-Daitoku.
These novel findings provide crucial information regarding the molecular and genetic landscape of highly pathogenic H. pylori and may assist in the development of innovative therapeutics for the treatment of H. pylori related illnesses, including gastric cancer.
Story Source:
Materials provided by Osaka University. Note: Content may be edited for style and length.
Journal Reference:
- Ryo Kinoshita-Daitoku, Kotaro Kiga, Masatoshi Miyakoshi, Ryota Otsubo, Yoshitoshi Ogura, Takahito Sanada, Zhu Bo, Tuan Vo Phuoc, Tokuju Okano, Tamako Iida, Rui Yokomori, Eisuke Kuroda, Sayaka Hirukawa, Mototsugu Tanaka, Arpana Sood, Phawinee Subsomwong, Hiroshi Ashida, Tran Thanh Binh, Lam Tung Nguyen, Khien Vu Van, Dang Quy Dung Ho, Kenta Nakai, Toshihiko Suzuki, Yoshio Yamaoka, Tetsuya Hayashi, Hitomi Mimuro. A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-22317-7
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