A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment

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 and Hitomi Mimuro ()
Additional contact information
Ryo Kinoshita-Daitoku: Osaka University
Kotaro Kiga: The University of Tokyo
Masatoshi Miyakoshi: University of Tsukuba
Ryota Otsubo: Osaka University
Yoshitoshi Ogura: Kyushu University
Takahito Sanada: Osaka University
Zhu Bo: The University of Tokyo
Tuan Vo Phuoc: Oita University
Tokuju Okano: Tokyo Medical and Dental University
Tamako Iida: The University of Tokyo
Rui Yokomori: The University of Tokyo
Eisuke Kuroda: Osaka University
Sayaka Hirukawa: The University of Tokyo
Mototsugu Tanaka: The University of Tokyo
Arpana Sood: The University of Tokyo
Phawinee Subsomwong: Osaka University
Hiroshi Ashida: Tokyo Medical and Dental University
Tran Thanh Binh: Oita University
Lam Tung Nguyen: Oita University
Khien Vu Van: Department of GI Endoscopy, 108 Central Hospital
Dang Quy Dung Ho: Department of Endoscopy, Cho Ray Hospital
Kenta Nakai: The University of Tokyo
Toshihiko Suzuki: Tokyo Medical and Dental University
Yoshio Yamaoka: Oita University
Tetsuya Hayashi: Kyushu University
Hitomi Mimuro: Osaka University

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Long-term infection of the stomach with Helicobacter pylori can cause gastric cancer. However, the mechanisms by which the bacteria adapt to the stomach environment are poorly understood. Here, we show that a small non-coding RNA of H. pylori (HPnc4160, also known as IsoB or NikS) regulates the pathogen’s adaptation to the host environment as well as bacterial oncoprotein production. In a rodent model of H. pylori infection, the genomes of bacteria isolated from the stomach possess an increased number of T-repeats upstream of the HPnc4160-coding region, and this leads to reduced HPnc4160 expression. We use RNA-seq and iTRAQ analyses to identify eight targets of HPnc4160, including genes encoding outer membrane proteins and oncoprotein CagA. Mutant strains with HPnc4160 deficiency display increased colonization ability of the mouse stomach, in comparison with the wild-type strain. Furthermore, HPnc4160 expression is lower in clinical isolates from gastric cancer patients than in isolates derived from non-cancer patients, while the expression of HPnc4160’s targets is higher in the isolates from gastric cancer patients. Therefore, the small RNA HPnc4160 regulates H. pylori adaptation to the host environment and, potentially, gastric carcinogenesis.

Date: 2021
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DOI: 10.1038/s41467-021-22317-7

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