Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation
Introduction:Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiot...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1335704/full |
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| author | Paula Roszczenko-Jasińska Artur Giełdoń Dominika Mazur Marta Spodzieja Maciej Plichta Cezary Czaplewski Wojciech Bal Elzbieta K. Jagusztyn-Krynicka Dariusz Bartosik |
| author_facet | Paula Roszczenko-Jasińska Artur Giełdoń Dominika Mazur Marta Spodzieja Maciej Plichta Cezary Czaplewski Wojciech Bal Elzbieta K. Jagusztyn-Krynicka Dariusz Bartosik |
| author_sort | Paula Roszczenko-Jasińska |
| collection | DOAJ |
| description | Introduction:Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiotic therapies face challenges due to increasing antibiotic resistance and patient non-compliance, necessitating the exploration of alternative treatment approaches. In this study, we focused on Hp0231 (DsbK), an essential component of the H. pylori Dsb (disulfide bond) oxidative pathway, and investigated peptide-based inhibition as a potential therapeutic strategy.Methods: Three inhibitory peptides designed by computational modeling were evaluated for their effectiveness using a time-resolved fluorescence assay. We also examined the binding affinity between Hp0231 and the peptides using microscale thermophoresis.Results and discussion: Our findings demonstrate that in silico-designed synthetic peptides can effectively inhibit Hp0231-mediated peptide oxidation. Targeting Hp0231 oxidase activity could attenuate H. pylori virulence without compromising bacterial viability. Therefore, peptide-based inhibitors of Hp0231 could be candidates for the development of new targeted strategy, which does not influence the composition of the natural human microbiome, but deprive the bacterium of its pathogenic properties. |
| first_indexed | 2024-03-08T14:43:36Z |
| format | Article |
| id | doaj.art-1b628f976fc34003815c9fe63d50ded5 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-03-08T14:43:36Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-1b628f976fc34003815c9fe63d50ded52024-01-11T15:26:34ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2024-01-011010.3389/fmolb.2023.13357041335704Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formationPaula Roszczenko-Jasińska0Artur Giełdoń1Dominika Mazur2Marta Spodzieja3Maciej Plichta4Cezary Czaplewski5Wojciech Bal6Elzbieta K. Jagusztyn-Krynicka7Dariusz Bartosik8Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, PolandFaculty of Chemistry, University of Gdańsk, Gdańsk, PolandDepartment of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, PolandFaculty of Chemistry, University of Gdańsk, Gdańsk, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, PolandFaculty of Chemistry, University of Gdańsk, Gdańsk, PolandInstitute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, PolandDepartment of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, PolandDepartment of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, PolandIntroduction:Helicobacter pylori is a bacterium that colonizes the gastric epithelium, which affects millions of people worldwide. H. pylori infection can lead to various gastrointestinal diseases, including gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Conventional antibiotic therapies face challenges due to increasing antibiotic resistance and patient non-compliance, necessitating the exploration of alternative treatment approaches. In this study, we focused on Hp0231 (DsbK), an essential component of the H. pylori Dsb (disulfide bond) oxidative pathway, and investigated peptide-based inhibition as a potential therapeutic strategy.Methods: Three inhibitory peptides designed by computational modeling were evaluated for their effectiveness using a time-resolved fluorescence assay. We also examined the binding affinity between Hp0231 and the peptides using microscale thermophoresis.Results and discussion: Our findings demonstrate that in silico-designed synthetic peptides can effectively inhibit Hp0231-mediated peptide oxidation. Targeting Hp0231 oxidase activity could attenuate H. pylori virulence without compromising bacterial viability. Therefore, peptide-based inhibitors of Hp0231 could be candidates for the development of new targeted strategy, which does not influence the composition of the natural human microbiome, but deprive the bacterium of its pathogenic properties.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1335704/fullHelicobacter pyloridisulfide bond proteinsHp0231 oxidoreductasepeptide-based inhibitorsDsb targeting inhibitorsstructure-based drug design |
| spellingShingle | Paula Roszczenko-Jasińska Artur Giełdoń Dominika Mazur Marta Spodzieja Maciej Plichta Cezary Czaplewski Wojciech Bal Elzbieta K. Jagusztyn-Krynicka Dariusz Bartosik Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation Frontiers in Molecular Biosciences Helicobacter pylori disulfide bond proteins Hp0231 oxidoreductase peptide-based inhibitors Dsb targeting inhibitors structure-based drug design |
| title | Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation |
| title_full | Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation |
| title_fullStr | Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation |
| title_full_unstemmed | Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation |
| title_short | Exploring the inhibitory potential of in silico-designed small peptides on Helicobacter pylori Hp0231 (DsbK), a periplasmic oxidoreductase involved in disulfide bond formation |
| title_sort | exploring the inhibitory potential of in silico designed small peptides on helicobacter pylori hp0231 dsbk a periplasmic oxidoreductase involved in disulfide bond formation |
| topic | Helicobacter pylori disulfide bond proteins Hp0231 oxidoreductase peptide-based inhibitors Dsb targeting inhibitors structure-based drug design |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1335704/full |
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