Mutational diversity in mutY deficient Helicobacter pylori and its effect on adaptation to the gastric environment

Kinoshita-Daitoku, Ryo; Kiga, Kotaro; Sanada, Takahito; Ogura, Yoshitoshi; Zhu, Bao‐Ku; Iida, Tamako; Yokomori, Rui; Kuroda, Eisuke; Tanaka, Mototsugu; Sood, Arpana; Suzuki, Toshihiko; Nakai, Kenta; Hayashi, Tetsuya; Mimuro, Hitomi

doi:10.1016/j.bbrc.2020.02.087

Cited by 6 publications

(2 citation statements)

References 36 publications

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“…Animal infection. H. pylori infection of rodents was performed as follows 31,32 . Briefly, 6-week-old male MON/Jms/GbsSlc Mongolian gerbils were orally administered 200 μL Vancomycin (500 mg/L) 24 and 48 h before H. pylori inoculation.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2021

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“…Notably, H. pylori mutY mutants demonstrate only 30% of the colonization efficiency compared to the wild‐type when infecting mouse stomachs 132 . Recently, Kinoshita et al 133 found that mutY −/− strains displayed a significantly elevated occurrence of spontaneous G:C to T:A mutations.…”

Section: Antioxidant Defenses Of H Pylorimentioning

confidence: 99%

Reactive oxygen species and gastric carcinogenesis: The complex interaction between Helicobacter pylori and host

Wu,

Chen,

Chen

et al. 2023

Helicobacter

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Helicobacter pylori (H. pylori) is a highly successful human pathogen that colonizes stomach in around 50% of the global population. The colonization of bacterium induces an inflammatory response and a substantial rise in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), mostly derived from host neutrophils and gastric epithelial cells, which play a crucial role in combating bacterial infections. However, H. pylori has developed various strategies to quench the deleterious effects of ROS, including the production of antioxidant enzymes, antioxidant proteins as well as blocking the generation of oxidants. The host's inability to eliminate H. pylori infection results in persistent ROS production. Notably, excessive ROS can disrupt the intracellular signal transduction and biological processes of the host, incurring chronic inflammation and cellular damage, such as DNA damage, lipid peroxidation, and protein oxidation. Markedly, the sustained inflammatory response and oxidative stress during H. pylori infection are major risk factor for gastric carcinogenesis. In this context, we summarize the literature on H. pylori infection‐induced ROS production, the strategies used by H. pylori to counteract the host response, and subsequent host damage and gastric carcinogenesis.

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Antibiotic-induced ROS-mediated Fur allosterism contributes to Helicobacter pylori resistance by inhibiting arsR activation of mutS and mutY

Xue,

Li,

Zhao

et al. 2024

Antimicrob Agents Chemother

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The increasing antibiotic resistance of Helicobacter pylori primarily driven by genetic mutations poses a significant clinical challenge. Although previous research has suggested that antibiotics could induce genetic mutations in H. pylori , the molecular mechanisms regulating the antibiotic induction remain unclear. In this study, we applied various techniques (e.g., fluorescence microscopy, flow cytometry, and multifunctional microplate reader) to discover that three different types of antibiotics could induce the intracellular generation of reactive oxygen species (ROS) in H. pylori . It is well known that ROS, a critical factor contributing to bacterial drug resistance, not only induces damage to bacterial genomic DNA but also inhibits the expression of genes associated with DNA damage repair, thereby increasing the mutation rate of bacterial genes and leading to drug resistance. However, further research is needed to explore the molecular mechanisms underlying the ROS inhibition of the expression of DNA damage repair-related genes in H. pylori . In this work, we validated that ROS could trigger an allosteric change in the iron uptake regulatory protein Fur, causing its transition from apo-Fur to holo-Fur, repressing the expression of the regulatory protein ArsR, ultimately causing the down-regulation of key DNA damage repair genes (e.g., mutS and mutY ); this cascade increased the genomic DNA mutation rate in H. pylori . This study unveils a novel mechanism of antibiotic-induced resistance in H. pylori , providing crucial insights for the prevention and control of antibiotic resistance in H. pylori .

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Mutational diversity in mutY deficient Helicobacter pylori and its effect on adaptation to the gastric environment

Cited by 6 publications

References 36 publications

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

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

Reactive oxygen species and gastric carcinogenesis: The complex interaction between Helicobacter pylori and host

Antibiotic-induced ROS-mediated Fur allosterism contributes to Helicobacter pylori resistance by inhibiting arsR activation of mutS and mutY

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