| 1. |
- Cheng, Liu, et al.
(author)
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The Helicobacter heilmannii hofE and hofF Genes are Essential for Colonization of the Gastric Mucosa and Play a Role in IL-1β-Induced Gastric MUC13 Expression
- 2016
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In: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 21:6, s. 504-522
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Journal article (peer-reviewed)abstract
- Background: Helicobacter heilmannii is a zoonotic bacterium associated with gastric disease in humans. We recently showed that H. heilmannii binds to human gastric mucins and epithelial cells and highlighted a potential role for the murine Muc13 mucin in gastric Helicobacter colonization. The aims of this study were to investigate the role of the H. heilmannii hof gene locus encoding HofH/F/E/G/C/D in adhesion to the gastric mucosa and induction of increased gastric Muc13 expression. Methods: Bacterial hof gene and host gene expression experiments, Helicobacter binding assays and experimental infection studies in mice were performed. H. pylori and its ΔhofF mutant were included for comparison. Results: Helicobacter heilmannii strains lacking HofE or HofF showed a clear decrease in binding to gastric mucins and epithelial cells as well as a lower gastric colonization level in the stomach of Balb/c mice at 4 and 9 weeks post-infection compared to the H. heilmannii wildtype strain. Interestingly, H. heilmannii ΔhofE and ΔhofF and H. pylori ΔhofF did not induce an increased expression of MUC13 in human gastric epithelial cells and of Muc13 in the stomach of mice. Finally, we demonstrated that IL-1β is induced in the stomach as a response to Helicobacter colonization which on its turn is involved in the expression of MUC13/Muc13 in the gastric epithelium. Conclusion: These novel results in Helicobacter research identified H. heilmannii HofE and HofF as adhesins and suggest an important role of H. heilmannii HofE and HofF and H. pylori HofF in IL-1β-induced gastric MUC13/Muc13 expression.
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| 2. |
- Flahou, Bram, et al.
(author)
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Evidence for a primate origin of zoonotic Helicobacter suis colonizing domesticated pigs.
- 2018
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In: The ISME journal. - : Springer Science and Business Media LLC. - 1751-7370 .- 1751-7362. ; 12:1, s. 77-86
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Journal article (peer-reviewed)abstract
- Helicobacter suis is the second most prevalent Helicobacter species in the stomach of humans suffering from gastric disease. This bacterium mainly inhabits the stomach of domesticated pigs, in which it causes gastric disease, but it appears to be absent in wild boars. Interestingly, it also colonizes the stomach of asymptomatic rhesus and cynomolgus monkeys. The origin of modern human-, pig- or non-human primate-associated H. suis strains in these respective host populations was hitherto unknown. Here we show that H. suis in pigs possibly originates from non-human primates. Our data suggest that a host jump from macaques to pigs happened between 100000 and 15000 years ago and that pig domestication has had a significant impact on the spread of H. suis in the pig population, from where this pathogen occasionally infects humans. Thus, in contrast to our expectations, H. suis appears to have evolved in its main host in a completely different way than its close relative Helicobacter pylori in humans.
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| 3. |
- Joosten, Myrthe, et al.
(author)
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Divergence between the highly virulent zoonotic pathogen Helicobacter heilmannii and its closest relative, the low virulent Helicobacter ailurogastricus sp. nov.
- 2016
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In: Infection and immunity. - 1098-5522. ; 84:1, s. 293-306
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Journal article (peer-reviewed)abstract
- Helicobacter heilmannii naturally colonizes the stomach of dogs and cats, and has been associated with gastric disorders in humans. Nine feline Helicobacter strains, classified as H. heilmannii based on ureAB and 16S rRNA gene sequences, were divided into a highly virulent and a low virulent group. The genomes of these strains were sequenced to investigate their phylogenetic relationships, to define their gene content and diversity and to determine if the differences in pathogenicity were associated with the presence/absence of potential virulence genes. The binding capacity of these helicobacters to the gastric mucosa was investigated as well.Our analyses revealed that the low virulent strains do not belong to the H. heilmannii species, but to a novel, closely related species for which we propose the name H. ailurogastricus. Several homologs of H. pylori virulence factors, such as IceA1, HrgA and jhp0562-like glycosyltransferase, are present in H. heilmannii but absent in H. ailurogastricus. Both species contain a VacA-like autotransporter, from which the passenger domain is remarkably larger for H. ailurogastricus compared to H. heilmannii. In addition, H. ailurogastricus shows clear differences in binding to the gastric mucosa compared to H. heilmannii. These findings highlight the low virulent character of this novel Helicobacter species.
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| 4. |
- Liu, Cheng, et al.
(author)
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Gastric de novo Muc13 expression and spasmolytic polypeptide-expressing metaplasia during Helicobacter heilmannii infection.
- 2014
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In: Infection and immunity. - 1098-5522. ; 82:8, s. 3227-39
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Journal article (peer-reviewed)abstract
- Helicobacter heilmannii is a zoonotic bacterium that has been associated with gastric disease in humans. In this study, the mRNA expression of mucins in the stomach of BALB/c mice was analyzed at several time points during a 1-year infection with this bacterium, during which gastric disease progressed in severity. Markers for acid production by parietal cells and mucous metaplasia were also examined. In the first 9 weeks postinfection, the mRNA expression of Muc6 was clearly upregulated in both the antrum and fundus of the stomach of H. heilmannii-infected mice. Interestingly, Muc13 was upregulated already at 1 day postinfection in the fundus of the stomach. Its expression level remained high in the stomach over the course of the infection. This mucin is, however, not expressed in a healthy stomach, and high expression of this mucin has so far only been described in gastric cancer. In the later stages of infection, mRNA expression of H(+)/K(+)-ATPase α/β and KCNQ1 decreased, whereas the expression of Muc4, Tff2, Dmbt1, and polymeric immunoglobulin receptor (pIgR) increased starting at 16 weeks postinfection onwards, suggesting the existence of spasmolytic polypeptide-expressing metaplasia in the fundus of the stomach. Mucous metaplasia present in the mucosa surrounding low-grade mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions was also histologically confirmed. Our findings indicate that H. heilmannii infection causes severe gastric pathologies and alterations in the expression pattern of gastric mucins, such as Muc6 and Muc13, as well as disrupting gastric homeostasis by inducing the loss of parietal cells, resulting in the development of mucous metaplasia.
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| 5. |
- Padra, Médea, 1986, et al.
(author)
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Helicobacter suis infection alters glycosylation and decreases the pathogen growth inhibiting effect and binding avidity of gastric mucins
- 2019
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In: Mucosal Immunology. - : Elsevier BV. - 1933-0219 .- 1935-3456. ; 12, s. 784-794
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Journal article (peer-reviewed)abstract
- © 2019, The Author(s). Helicobacter suis is the most prevalent non-Helicobacter pylori Helicobacter species in the human stomach and is associated with chronic gastritis, peptic ulcer disease, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. H. suis colonizes the gastric mucosa of 60–95% of pigs at slaughter age, and is associated with chronic gastritis, decreased weight gain, and ulcers. Here, we show that experimental H. suis infection changes the mucin composition and glycosylation, decreasing the amount of H. suis-binding glycan structures in the pig gastric mucus niche. Similarly, the H. suis-binding ability of mucins from H. pylori-infected humans is lower than that of noninfected individuals. Furthermore, the H. suis growth-inhibiting effect of mucins from both noninfected humans and pigs is replaced by a growth-enhancing effect by mucins from infected individuals/pigs. Thus, Helicobacter spp. infections impair the mucus barrier by decreasing the H. suis-binding ability of the mucins and by decreasing the antiprolific activity that mucins can have on H. suis. Inhibition of these mucus-based defenses creates a more stable and inhabitable niche for H. suis. This is likely of importance for long-term colonization and outcome of infection, and reversing these impairments may have therapeutic benefits.
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