scholarly journals Variations in Helicobacter pylori Lipopolysaccharide To Evade the Innate Immune Component Surfactant Protein D

2005 ◽  
Vol 73 (11) ◽  
pp. 7677-7686 ◽  
Author(s):  
Wafa Khamri ◽  
Anthony P. Moran ◽  
Mulugeta L. Worku ◽  
Q. Najma Karim ◽  
Marjorie M. Walker ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Phase Variation ◽  
Surfactant Protein ◽  
Clinical Isolates ◽  
Surfactant Protein D ◽  
Human Gastric Mucosa ◽  
H Pylori

ABSTRACT Helicobacter pylori is a common and persistent human pathogen of the gastric mucosa. Surfactant protein D (SP-D), a component of innate immunity, is expressed in the human gastric mucosa and is capable of aggregating H. pylori. Wide variation in the SP-D binding affinity to H. pylori has been observed in clinical isolates and laboratory-adapted strains. The aim of this study was to reveal potential mechanisms responsible for evading SP-D binding and establishing persistent infection. An escape variant, J178V, was generated in vitro, and the lipopolysaccharide (LPS) structure of the variant was compared to that of the parental strain, J178. The genetic basis for structural variation was explored by sequencing LPS biosynthesis genes. SP-D binding to clinical isolates was demonstrated by fluorescence-activated cell sorter analyses. Here, we show that H. pylori evades SP-D binding through phase variation in lipopolysaccharide. This phenomenon is linked to changes in the fucosylation of the O chain, which was concomitant with slipped-strand mispairing in a poly(C) tract of the fucosyltransferase A (fucT1) gene. SP-D binding organisms are predominant in mucus in vivo (P = 0.02), suggesting that SP-D facilitates physical elimination. Phase variation to evade SP-D contributes to the persistence of this common gastric pathogen.

Living cells of probiotic Bifidobacterium bifidum YIT 10347 detected on gastric mucosa in humans

2016 ◽  
Vol 7 (3) ◽  
pp. 319-326 ◽  
Author(s):  
H. Shibahara-Sone ◽  
A. Gomi ◽  
T. Iino ◽  
M. Kano ◽  
C. Nonaka ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Human Study ◽  
In Vitro Study ◽  
Probiotic Strain ◽  
Bifidobacterium Bifidum ◽  
Human Gastric Mucosa ◽  
Beneficial Effects ◽  
H Pylori

The probiotic strain Bifidobacterium bifidum YIT 10347 has been demonstrated to inhibit Helicobacter pylori activity, prevent injury to the gastric mucosa, and improve general gastric malaise symptoms in H. pylori positive patients. This study aimed to investigate the adhering activity and localisation of B. bifidum YIT 10347 to gastric cells and tissue in vitro, and in human in vivo to clarify the mechanism of its beneficial effects on the stomach. The in vitro study found the adhesion rate of B. bifidum YIT 10347 to human gastric epithelial cells was about 10 times higher than that of lactic acid bacteria and other bifidobacteria. In the human study, 5 H. pylori negative and 12 H. pylori positive subjects ingested milk fermented with B. bifidum YIT 10347. B. bifidum YIT 10347 cells were measured by RT-qPCR for in gastric biopsy samples. Living B. bifidum YIT 10347 cells were detected in the biopsy samples in H. pylori negative subjects (105 cells/g and 104 cells/g at 1 h and 2 h after ingestion, respectively) and H. pylori positive subjects (104 cells/g at 1 h after the ingestion). Moreover, immunostaining analysis of tissue sections found that B. bifidum YIT 10347 cells were located at the interstitial mucin layer of the stomach. These results suggest that cells of probiotic B. bifidum YIT 10347 adhered to the human gastric mucosa in a live state, and that the higher adhering activity of B. bifidum YIT 10347 to the gastric mucosa may be involved in its beneficial effects on the human stomach.

scholarly journals In Vitro and In Vivo Antibacterial Activities of Patchouli Alcohol, a Naturally Occurring Tricyclic Sesquiterpene, against Helicobacter pylori Infection

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Y. F. Xu ◽  
D. W. Lian ◽  
Y. Q. Chen ◽  
Y. F. Cai ◽  
Y. F. Zheng ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Bacterial Resistance ◽  
Clinical Isolates ◽  
Potential Candidate ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Patchouli Alcohol ◽  
H Pylori

ABSTRACT This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activities and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In the in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and on 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB, and babA genes), motility (and its flaA and flaB genes), ultrastructure, and flagellation were investigated. Moreover, the H. pylori resistance to and postantibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3 to 9) and 12 clinical isolates were 25 to 75 and 12.5 to 50 μg/ml, respectively. The killing kinetics of PA were time and concentration dependent, and its minimal bactericidal concentrations (MBCs) were 25 to 75 μg/ml. In addition, H. pylori adhesion, motility, ultrastructure, and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB) and motility genes (flaA and flaB). Furthermore, PA treatment caused a longer PAE and less bacterial resistance than clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (COX-2, interleukin 1β, tumor necrosis factor alpha, and inducible nitric oxide synthase [iNOS]). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process, and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development.

scholarly journals In Vitro and In Vivo Inhibition of Helicobacter pylori by Lactobacillus casei Strain Shirota

2004 ◽  
Vol 70 (1) ◽  
pp. 518-526 ◽  
Author(s):  
D. Sgouras ◽  
P. Maragkoudakis ◽  
K. Petraki ◽  
B. Martinez-Gonzalez ◽  
E. Eriotou ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Lactobacillus Casei ◽  
Clinical Isolates ◽  
Mucosal Inflammation ◽  
Control Group ◽  
Study Group ◽  
Milk Product ◽  
H Pylori

ABSTRACT We studied the potential inhibitory effect of Lactobacillus casei strain Shirota (from the fermented milk product Yakult [Yakult Ltd., Tokyo, Japan]) on Helicobacter pylori by using (i) in vitro inhibition assays with H. pylori SS1 (Sydney strain 1) and nine H. pylori clinical isolates and (ii) the in vivo H. pylori SS1 mouse model of infection over a period of 9 months. In vitro activity against H. pylori SS1 and all of the clinical isolates was observed in the presence of viable L. casei strain Shirota cells but not in the cell-free culture supernatant, although there was profound inhibition of urease activity. In vivo experiments were performed by oral administration of L. casei strain Shirota in the water supply over a period of 9 months to 6-week-old C57BL/6 mice previously infected with H. pylori SS1 (study group; n = 25). Appropriate control groups of H. pylori-infected but untreated animals (n = 25) and uninfected animals given L. casei strain Shirota (n = 25) also were included in the study. H. pylori colonization and development of gastritis were assessed at 1, 2, 3, 6, and 9 months postinfection. A significant reduction in the levels of H. pylori colonization was observed in the antrum and body mucosa in vivo in the lactobacillus-treated study group, as assessed by viable cultures, compared to the levels in the H. pylori-infected control group. This reduction was accompanied by a significant decline in the associated chronic and active gastric mucosal inflammation observed at each time point throughout the observation period. A trend toward a decrease in the anti-H. pylori immunoglobulin G response was measured in the serum of the animals treated with lactobacillus, although this decrease was not significant.

scholarly journals Limited Role of Lipopolysaccharide Lewis Antigens in Adherence of Helicobacter pylori to the Human Gastric Epithelium

2003 ◽  
Vol 71 (5) ◽  
pp. 2876-2880 ◽  
Author(s):  
Jafar Mahdavi ◽  
Thomas Borén ◽  
Christina Vandenbroucke-Grauls ◽  
Ben J. Appelmelk
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Epithelium ◽  
In Vivo Studies ◽  
Minor Role ◽  
Human Gastric Mucosa ◽  
H Pylori

ABSTRACT In vitro and in vivo studies from various groups have suggested that Helicobacter pylori lipopolysaccharide (LPS) Lewis x (Lex) antigens mediate bacterial adhesion. We have now reevaluated this hypothesis by studying the adherence in situ of H. pylori strain 11637 and its corresponding Lex-negative rfbM mutant to human gastric mucosa from patients (n = 22) with various gastric pathologies. Significant binding of the parent strain was observed in only 8 out of 22 sections; in four out of eight patients, the Lex-negative mutant bound less well. One of these four patients displayed no gastric abnormalities, and the other three showed dysplasia, metaplasia, and adenocarcinoma, respectively; hence, we are unable to define the circumstances under which LPS-mediated adhesion takes place. We conclude that H. pylori LPS plays a distinct but minor role in adhesion.

scholarly journals Expression of Surfactant Protein D in the Human Gastric Mucosa and during Helicobacter pylori Infection

2002 ◽  
Vol 70 (3) ◽  
pp. 1481-1487 ◽  
Author(s):  
Emma Murray ◽  
Wafa Khamri ◽  
Marjorie M. Walker ◽  
Paul Eggleton ◽  
Anthony P. Moran ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Surfactant Protein ◽  
Normal Mucosa ◽  
Innate Immune ◽  
Surfactant Protein D ◽  
Human Gastric Mucosa ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Immune Molecule ◽  
H Pylori

ABSTRACT Helicobacter pylori establishes persistent infection of gastric mucosa with diverse clinical outcomes. The innate immune molecule surfactant protein D (SP-D) binds selectively to microorganisms, inducing aggregation and phagocytosis. In this study, we demonstrated the expression of SP-D in gastric mucosa by reverse transcription-PCR and immuohistochemical analysis. SP-D is present at the luminal surface and within the gastric pits, with maximal expression at the surface. Levels of expression are significantly increased in H. pylori-associated gastritis compared to those in the normal mucosa. Immunofluorescence microscopy was used to demonstrate binding and agglutination of H. pylori by SP-D in a lectin-specific manner. These activities resulted in a 50% reduction in the motility of H. pylori, as judged on the basis of curvilinear velocity measured by using a Hobson BacTracker. Lipopolysaccharides extracted from three H. pylori strains were shown to bind SP-D in a concentration-dependent manner, and there was marked variation in the avidity of binding among the strains. SP-D may therefore play a significant role in the innate immune response to H. pylori infection.

scholarly journals Cholestenone functions as an antibiotic against Helicobacter pylori by inhibiting biosynthesis of the cell wall component CGL

2021 ◽  
Vol 118 (16) ◽  
pp. e2016469118
Author(s):  
Junichi Kobayashi ◽  
Masatomo Kawakubo ◽  
Chifumi Fujii ◽  
Nobuhiko Arisaka ◽  
Masaki Miyashita ◽  
...  
Keyword(s):  
Cell Wall ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Control Diet ◽  
Inhibitory Effects ◽  
Oral Medicine ◽  
Resistant Strains ◽  
H Pylori

Helicobacter pylori, a pathogen responsible for gastric cancer, contains a unique glycolipid, cholesteryl-α-D-glucopyranoside (CGL), in its cell wall. Moreover, O-glycans having α1,4-linked N-acetylglucosamine residues (αGlcNAc) are secreted from gland mucous cells of gastric mucosa. Previously, we demonstrated that CGL is critical for H. pylori survival and that αGlcNAc serves as antibiotic against H. pylori by inhibiting CGL biosynthesis. In this study, we tested whether a cholesterol analog, cholest-4-en 3-one (cholestenone), exhibits antibacterial activity against H. pylori in vitro and in vivo. When the H. pylori standard strain ATCC 43504 was cultured in the presence of cholestenone, microbial growth was significantly suppressed dose-dependently relative to microbes cultured with cholesterol, and cholestenone inhibitory effects were not altered by the presence of cholesterol. Morphologically, cholestenone-treated H. pylori exhibited coccoid forms. We obtained comparable results when we examined the clarithromycin-resistant H. pylori strain “2460.” We also show that biosynthesis of CGL and its derivatives cholesteryl-6-O-tetradecanoyl-α-D-glucopyranoside and cholesteryl-6-O-phosphatidyl-α-D-glucopyranoside in H. pylori is remarkably inhibited in cultures containing cholestenone. Lastly, we asked whether orally administered cholestenone eradicated H. pylori strain SS1 in C57BL/6 mice. Strikingly, mice fed a cholestenone-containing diet showed significant eradication of H. pylori from the gastric mucosa compared with mice fed a control diet. These results overall strongly suggest that cholestenone could serve as an oral medicine to treat patients infected with H. pylori, including antimicrobial-resistant strains.

scholarly journals Helicobacter pylori-induced Rev-erbα fosters gastric bacterial colonization by impairing host innate and adaptive defense

2020 ◽  
Author(s):  
Yuan Zhuang ◽  
Fangyuan Mao ◽  
Yipin Lv ◽  
Chuanjie Hao ◽  
Yongsheng Teng ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Bacterial Colonization ◽  
Direct Consequence ◽  
Gastric Epithelium ◽  
Th1 Cell ◽  
Extracellular Signal ◽  
H Pylori

Abstract Background: Helicobacter pylori (H. pylori) is a human pathogen that infects nearly half of the world’s population, however, the persistent colonization of H. pylori in gastric mucosa remains poorly understood. Nowadays it is believed that impairment of host defense of gastric epithelium induced by H. pylori plays key roles in H. pylori-associated pathology. The nuclear receptor Rev-erbα represents a powerful transcriptional repressor involved in host immunity. However, the regulation, function, and clinical relevance of Rev-erbα in H. pylori infection are presently unknown. Here we demonstrated a pro-colonization role of Rev-erbα in H. pylori infection.Results: Rev-erbα was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced gastric epithelial cells (GECs) to express Rev-erbα via the phosphorylated cagA that activated extracellular signal-regulated kinase (ERK) signaling pathway to mediate transcription factor nuclear factor kappa-B (NF-κB) directly binding to Rev-erbα promoter. Human gastric Rev-erbα expression correlated with H. pylori colonization, and mouse Rev-erbα from non-bone marrow-derived cells promoted gastric H. pylori burden. Importantly, H. pylori colonization was attenuated in Rev-erbα-/- mice and the mice with in vivo pharmacological inhibition of Rev-erbα. Mechanistically, Rev-erbα in GECs not only directly suppressed Reg3b and β-defensin-1 expression via binding to Reg3b and β-defensin-1 promoter respectively, which resulted in impaired bactericidal effects against H. pylori of these antibacterial proteins in vitro and in vivo; but also directly inhibited chemokine CCL21 expression via binding to CCL21 promoter, which led to decreased gastric influx of CD45+CD11c-Ly6G-CD11b+CD68- myeloid cells by CCL21-CCR7-dependent migration and, as a direct consequence, reduced bacterial clearing capacity of H. pylori-specific T helper type 1 (Th1) cell response. Conclusions: Overall, this study identifies a model involving Rev-erbα, which collectively ensures gastric bacterial persistence by suppressing host gene expression required for local innate and adaptive defense against H. pylori, and also highlight a pathological role and an immunosuppressive mechanism of Rev-erbα in persistent H. pylori infection.

scholarly journals Adherence ofHelicobacter pylorito the Gastric Mucosa

1997 ◽  
Vol 11 (3) ◽  
pp. 243-248 ◽  
Author(s):  
Marguerite Clyne ◽  
Brendan Drumm
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Bacterial Adhesion ◽  
Initial Step ◽  
Gastric Epithelium ◽  
In Vivo Models ◽  
Enteric Diseases ◽  
H Pylori

Bacterial adhesion to the intestinal epithelium is a critical initial step in the pathogenesis of many enteric diseases.Helicobacter pyloriis a duodenal pathogen that adheres to the gastric epithelium and causes gastritis and peptic ulceration. The mechanism by whichH pyloricauses disease has not yet been elucidated but adherence to the gastric mucosa is thought to be an important virulence determinant of the organism. What is known about adherence ofH pylorito the gastric mucosa is summarized. Topics discussed are the mechanism ofH pyloriadherence; in vitro and in vivo models ofH pyloriinfection; and adherence and potential adhesins and receptors forH pylori.

Enhanced fitness of a Helicobacter pylori babA mutant in a murine model

2021 ◽  
Author(s):  
M. Lorena Harvey ◽  
Aung Soe Lin ◽  
Lili Sun ◽  
Tatsuki Koyama ◽  
Jennifer H. B. Shuman ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Outer Membrane Proteins ◽  
Population Diversity ◽  
Fitness Advantage ◽  
Neutral Locus ◽  
Mutant Strains ◽  
Bacterial Fitness ◽  
H Pylori

Helicobacter pylori genomes encode >60 predicted outer membrane proteins (OMPs). Several OMPs in the Hop family act as adhesins, but the functions of most Hop proteins are unknown. To identify hop mutant strains that exhibit altered fitness in vivo compared to fitness in vitro , we used a genetic barcoding method that allowed us to track changes in the proportional abundance of H. pylori strains within a mixed population. We generated a library of hop mutant strains, each containing a unique nucleotide barcode, as well as a library of control strains, each containing a nucleotide barcode in an intergenic region predicted to be a neutral locus unrelated to bacterial fitness. We orogastrically inoculated each of the libraries into mice and analyzed compositional changes in the populations over time in vivo compared to changes detected in the populations during library passage in vitro . The control library proliferated as a relatively stable community in vitro, but there was a reduction in the population diversity of this library in vivo and marked variation in the dominant strains recovered from individual animals, consistent with the existence of a non-selective bottleneck in vivo . We did not identify any OMP mutants exhibiting fitness defects exclusively in vivo without corresponding fitness defects in vitro . Conversely, a babA mutant exhibited a strong fitness advantage in vivo but not in vitro . These findings, when taken together with results of other studies, suggest that production of BabA may have differential effects on H. pylori fitness depending on the environmental conditions.

scholarly journals Lactobacillus johnsonii La1 Attenuates Helicobacter pylori-Associated Gastritis and Reduces Levels of Proinflammatory Chemokines in C57BL/6 Mice

2005 ◽  
Vol 12 (12) ◽  
pp. 1378-1386 ◽  
Author(s):  
Dionyssios N. Sgouras ◽  
Effrosini G. Panayotopoulou ◽  
Beatriz Martinez-Gonzalez ◽  
Kalliopi Petraki ◽  
Spyros Michopoulos ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Lamina Propria ◽  
Serum Levels ◽  
Favorable Effect ◽  
Lactobacillus Johnsonii ◽  
Ags Cells ◽  
Inflammatory Infiltration ◽  
H Pylori

ABSTRACT In clinical settings, Lactobacillus johnsonii La1 administration has been reported to have a favorable effect on Helicobacter pylori-associated gastritis, although the mechanism remains unclear. We administered, continuously through the water supply, live La1 to H. pylori-infected C57BL/6 mice and followed colonization, the development of H. pylori-associated gastritis in the lamina propria, and the levels of proinflammatory chemokines macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived cytokine (KC) in the serum and gastric tissue over a period of 3 months. We documented a significant attenuation in both lymphocytic (P = 0.038) and neutrophilic (P = 0.003) inflammatory infiltration in the lamina propria as well as in the circulating levels of anti-H. pylori immunoglobulin G antibodies (P = 0.003), although we did not observe a suppressive effect of La1 on H. pylori colonizing numbers. Other lactobacilli, such as L. amylovorus DCE 471 and L. acidophilus IBB 801, did not attenuate H. pylori-associated gastritis to the same extent. MIP-2 serum levels were distinctly reduced during the early stages of H. pylori infection in the La1-treated animals, as were gastric mucosal levels of MIP-2 and KC. Finally, we also observed a significant reduction (P = 0.046) in H. pylori-induced interleukin-8 secretion by human adenocarcinoma AGS cells in vitro in the presence of neutralized (pH 6.8) La1 spent culture supernatants, without concomitant loss of H. pylori viability. These observations suggest that during the early infection stages, administration of La1 can attenuate H. pylori-induced gastritis in vivo, possibly by reducing proinflammatory chemotactic signals responsible for the recruitment of lymphocytes and neutrophils in the lamina propria.

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