Journal article
Positive selection of mutations in the Helicobacter pylori katA 5′ untranslated region in a Mongolian Gerbil Model of gastric disease
Infection and Immunity, Vol.90(7), Art. e0000422
2022
Abstract
To evaluate potential effects of gastric inflammation on Helicobacter pylori diversification and evolution within the stomach, we experimentally infected Mongolian gerbils with an H. pylori strain in which Cag type IV secretion system (T4SS) activity is controlled by a TetR/tetO system. Gerbils infected with H. pylori under conditions in which Cag T4SS activity was derepressed had significantly higher levels of gastric inflammation than gerbils infected under conditions with repressed Cag T4SS activity. Mutations in the 5′ untranslated region (UTR) of katA (encoding catalase) were detected in strains cultured from 8 of the 17 gerbils infected with Cag T4SS-active H. pylori and none of the strains from 17 gerbils infected with Cag T4SS-inactive H. pylori. Catalase enzymatic activity, steady-state katA transcript levels, and katA transcript stability were increased in strains with these single nucleotide polymorphisms (SNPs) compared to strains in which these SNPs were absent. Moreover, strains harboring these SNPs exhibited increased resistance to bactericidal effects of hydrogen peroxide, compared to control strains. Experimental introduction of the SNPs into the wild-type katA 5′ UTR resulted in increased katA transcript stability, increased katA steady-state levels, and increased catalase enzymatic activity. Based on site-directed mutagenesis and modeling of RNA structure, increased katA transcript levels were correlated with higher predicted thermal stability of the katA 5′ UTR secondary structure. These data suggest that high levels of gastric inflammation positively select for H. pylori strains producing increased levels of catalase, which may confer survival advantages to the bacteria in an inflammatory gastric environment.
Details
- Title
- Positive selection of mutations in the Helicobacter pylori katA 5′ untranslated region in a Mongolian Gerbil Model of gastric disease
- Authors/Creators
- J.T. Loh (Author/Creator) - Vanderbilt UniversityJ.H.B. Shuman (Author/Creator) - Vanderbilt University Medical CenterA.S. Lin (Author/Creator) - Vanderbilt University Medical CenterN. Favret (Author/Creator) - Vanderbilt University Medical CenterM.B. Piazuelo (Author/Creator) - Vanderbilt UniversityS. Mallal (Author/Creator) - Vanderbilt UniversityA. Chopra (Author/Creator) - Murdoch UniversityM.S. McClain (Author/Creator) - Vanderbilt UniversityT.L. Cover (Author/Creator) - Vanderbilt UniversityI.E. Brodsky (Author/Creator)
- Publication Details
- Infection and Immunity, Vol.90(7), Art. e0000422
- Publisher
- American Society for Microbiology
- Identifiers
- 991005542493907891
- Copyright
- © 2022 American Society for Microbiology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
24 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.95 Gastrointestinal & Esophageal Diseases
- 1.95.387 Helicobacter Pylori
- Web Of Science research areas
- Immunology
- Infectious Diseases
- ESI research areas
- Immunology