Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i>
<p dir="ltr"><i>Helicobacter pylori</i> is a pathogenic bacterium associated with developing gastric cancer and other gastric disorders. One of its major virulence factors, lipopolysaccharide (LPS), plays a crucial role in maintaining bacterial integrity, mediating host a...
محفوظ في:
| المؤلف الرئيسي: | |
|---|---|
| منشور في: |
2025
|
| الموضوعات: | |
| الوسوم: |
إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
|
| _version_ | 1852023832105189376 |
|---|---|
| author | Mou-Chieh Kao (18952576) |
| author_facet | Mou-Chieh Kao (18952576) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mou-Chieh Kao (18952576) |
| dc.date.none.fl_str_mv | 2025-01-08T03:13:15Z |
| dc.identifier.none.fl_str_mv | 10.6084/m9.figshare.28081937.v1 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/dataset/Roles_of_the_lipopolysaccharide_biosynthesis-related_gene_i_HP0858_i_in_the_fitness_of_i_Helicobacter_pylori_i_and_its_virulence_in_i_Galleria_mellonella_i_/28081937 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Bacteriology Helicobacter pylori lipopolysaccharide ADP-heptose bi-functional kinase/adenylyltransferase (RfaE/HldE/HP0858) adhesin AlpA protein glycosylation Galleria mellonella bacterial virulence drug target |
| dc.title.none.fl_str_mv | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i> |
| dc.type.none.fl_str_mv | Dataset info:eu-repo/semantics/publishedVersion dataset |
| description | <p dir="ltr"><i>Helicobacter pylori</i> is a pathogenic bacterium associated with developing gastric cancer and other gastric disorders. One of its major virulence factors, lipopolysaccharide (LPS), plays a crucial role in maintaining bacterial integrity, mediating host adhesion, and modulating the immune response. Recent studies have indicated that ADP-heptose, an intermediate in the heptose biosynthetic pathway involved in LPS synthesis cascade, is a novel pathogen-associated molecular pattern for <i>H. pylori</i>. This study focuses on the <i>HP0858</i> gene, which is predicted to encode RfaE/HldE, an enzyme with kinase and ADP-transferase activities essential for heptose production. An <i>HP0858</i> gene-disrupted mutant was first generated, and the resulting mutant exhibited a truncated LPS structure, confirming its role in LPS biosynthesis. The <i>HP0858</i>-deficient mutant displayed increased sensitivity to the detergent SDS and the antibiotic novobiocin, heightened surface hydrophobicity, and a propensity for autoaggregation. Additionally, the mutant exhibited reduced adhesion and internalization capabilities, a diminished elongation phenotype, and a failure to induce IL-8 secretion in infected gastric AGS cells. In an <i>in vivo</i> <i>Galleria mellonella</i> infection model, the <i>HP0858</i> knockout mutant showed significantly attenuated virulence, as no bacterial load was detectable in the larvae’s hemolymph 48 h post-infection, unlike the wild-type strain. Finally, we provided evidence that the enzyme encoded by <i>HP0858</i> is involved in a general protein glycosylation system linked to LPS biosynthesis, specifically glycosylating the adhesin AlpA. These findings highlight the essential role of RfaE/HldE/HP0858 in LPS biosynthesis and bacterial virulence, making it a promising target for future therapeutic interventions against <i>H. pylori</i> infections.</p> |
| eu_rights_str_mv | openAccess |
| id | Manara_fbbefde324ffc1d2ca8e78fcc8d86cc4 |
| identifier_str_mv | 10.6084/m9.figshare.28081937.v1 |
| network_acronym_str | Manara |
| network_name_str | ManaraRepo |
| oai_identifier_str | oai:figshare.com:article/28081937 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i>Mou-Chieh Kao (18952576)BacteriologyHelicobacter pylorilipopolysaccharideADP-heptosebi-functional kinase/adenylyltransferase (RfaE/HldE/HP0858)adhesin AlpAprotein glycosylationGalleria mellonellabacterial virulencedrug target<p dir="ltr"><i>Helicobacter pylori</i> is a pathogenic bacterium associated with developing gastric cancer and other gastric disorders. One of its major virulence factors, lipopolysaccharide (LPS), plays a crucial role in maintaining bacterial integrity, mediating host adhesion, and modulating the immune response. Recent studies have indicated that ADP-heptose, an intermediate in the heptose biosynthetic pathway involved in LPS synthesis cascade, is a novel pathogen-associated molecular pattern for <i>H. pylori</i>. This study focuses on the <i>HP0858</i> gene, which is predicted to encode RfaE/HldE, an enzyme with kinase and ADP-transferase activities essential for heptose production. An <i>HP0858</i> gene-disrupted mutant was first generated, and the resulting mutant exhibited a truncated LPS structure, confirming its role in LPS biosynthesis. The <i>HP0858</i>-deficient mutant displayed increased sensitivity to the detergent SDS and the antibiotic novobiocin, heightened surface hydrophobicity, and a propensity for autoaggregation. Additionally, the mutant exhibited reduced adhesion and internalization capabilities, a diminished elongation phenotype, and a failure to induce IL-8 secretion in infected gastric AGS cells. In an <i>in vivo</i> <i>Galleria mellonella</i> infection model, the <i>HP0858</i> knockout mutant showed significantly attenuated virulence, as no bacterial load was detectable in the larvae’s hemolymph 48 h post-infection, unlike the wild-type strain. Finally, we provided evidence that the enzyme encoded by <i>HP0858</i> is involved in a general protein glycosylation system linked to LPS biosynthesis, specifically glycosylating the adhesin AlpA. These findings highlight the essential role of RfaE/HldE/HP0858 in LPS biosynthesis and bacterial virulence, making it a promising target for future therapeutic interventions against <i>H. pylori</i> infections.</p>2025-01-08T03:13:15ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.6084/m9.figshare.28081937.v1https://figshare.com/articles/dataset/Roles_of_the_lipopolysaccharide_biosynthesis-related_gene_i_HP0858_i_in_the_fitness_of_i_Helicobacter_pylori_i_and_its_virulence_in_i_Galleria_mellonella_i_/28081937CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/280819372025-01-08T03:13:15Z |
| spellingShingle | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i> Mou-Chieh Kao (18952576) Bacteriology Helicobacter pylori lipopolysaccharide ADP-heptose bi-functional kinase/adenylyltransferase (RfaE/HldE/HP0858) adhesin AlpA protein glycosylation Galleria mellonella bacterial virulence drug target |
| status_str | publishedVersion |
| title | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i> |
| title_full | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i> |
| title_fullStr | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i> |
| title_full_unstemmed | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i> |
| title_short | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i> |
| title_sort | Roles of the lipopolysaccharide biosynthesis-related gene <i>HP0858</i> in the fitness of <i>Helicobacter pylori </i>and its virulence in <i>Galleria mellonella</i> |
| topic | Bacteriology Helicobacter pylori lipopolysaccharide ADP-heptose bi-functional kinase/adenylyltransferase (RfaE/HldE/HP0858) adhesin AlpA protein glycosylation Galleria mellonella bacterial virulence drug target |