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...
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2025
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| Summary: | <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> |
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