Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis

Yeh, Jia Yin; Lin, Hwai Jeng; Kuo, Chia Jung; Feng, Chun; Chou, Chia Huei; Lin, Chia Der; Wu, Hui; Li, Chen Yi; Chiu, Cheng Hsun; Lai, Chih Ho

doi:10.3389/fcell.2020.617419

Cited by 8 publications

(5 citation statements)

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“…Our previous studies demonstrated that statin use significantly reduced the incidence of H. pylori -related diseases [ 41 , 44 , 45 ]. Moreover, hijacking cholesterol by antagonists competed for VacA and CagA actions via lipid rafts alleviated H. pylori -induced pathogenesis [ 46 ]. Consistent with these findings, the present study showed that depletion of cholesterol interferes with H. pylori adherence and internalization into cells, which depends on CGT.…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori cholesterol-α-glucosyltransferase manipulates cholesterol for bacterial adherence to gastric epithelial cells

et al. 2021

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Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcers, and gastric cancer. Infection of cells with H. pylori is dependent on lipid rafts, which are cholesterol-rich microdomains located in the cell membrane. H. pylori cholesterol-α-glucosyltransferase (CGT) catalyzes the conversion of membrane cholesterol to cholesteryl glucosides, which can be incorporated into the bacterial cell wall, facilitating evasion from immune defense and colonization in the host. However, the detailed mechanisms underlying this process remain to be explored. In this study, we discovered for the first time that H. pylori CGT could promote adherence to gastric epithelial cells in a cholesterol-dependent manner. Externalization of cell membrane phosphatidylserine (PS) is crucial for enhancement of binding of H. pylori to cells by CGT and for cytotoxin-associated gene A (CagA)-induced pathogenesis. Furthermore, exogenous cholesterol interferes with the actions of H. pylori CGT to catalyze cellular cholesterol, which impedes bacterial binding to cells and attenuates subsequent inflammation, indicating that the initial attachment of H. pylori to cells is closely dependent on host cholesterol. These results provide evidence that CGT contributes to H. pylori infectivity and it may serve as a key target for the treatment of H. pylori -associated diseases.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori cholesterol-α-glucosyltransferase manipulates cholesterol for bacterial adherence to gastric epithelial cells

et al. 2021

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“…CdtA/CdtC bound to the lipid rafts and cholesterol-rich microdomains within the host cell membranes [ 50 ], and there was also a report that CdtA was not essential in this process [ 51 ]. Inactivation of CdtC confirmed its role in establishing infection and ameliorates H. pylori -induced pathogenesis by hijacking cholesterol [ 52 , 53 ]. Interestingly, C. upsaliensis was reported to produce higher CDT titre than other Campylobacter [ 40 ].…”

Section: Discussionmentioning

confidence: 98%

Genetic characteristics and potential pathogenic agents in Campylobacter upsaliensis based on genomic analysis

Wang,

Gu,

et al. 2024

Emerging Microbes & Infections

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Campylobacter upsaliensis was the most common Campylobacter species in pets’ gastrointestinal tracts and has been isolated from patients with bacteremia, hemolytic-uremic syndrome, spontaneous abortion, and Guillain-Barré syndrome. However, the genetic characteristics and the full extent of its significance as a human pathogen remain to be fully understood. This study involved an investigation for genomic analysis of 154 strains from different sources and additional antimicrobial resistance profiles of 26 strains for this species. The genomes contained 1,558–1,971 CDS and the genome sizes were estimated to vary from 1.53 Mb to 1.86 Mb, with an average GC content of 34.71%. The entire analyzed genomes could be divided into three clades (A, B, and C) based on ANI and phylogenomic analysis. Significantly, nearly all strains in Clade B were isolated from patient samples, and the virulence-related sequences FlgD, GmhA, and CdtC might serve as determining factors for the classification of Clade B. Half of the tested isolates had MIC values over 64 μg mL −1 for nalidixic acid, gentamicin, and streptomycin. Isolates from pets in China carried more resistant elements in the genomes. This study both provided a comprehensive profile of C. upsaliensis for its genomic features and suggested some pathogenic agents for human infection with this species.

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“…AGS cells were pretreated with P. goldsteinii MTS01 (MOI = 200) followed by infection with H. pylori (MOI = 100) for 6 h. H. pylori VacA-induced cell vacuolation and CagA-induced elongated cells (hummingbird phenotype) were observed. The percentage of elongated cells was determined as reported previously ( 29 ).…”

Section: Methodsmentioning

confidence: 99%

“…AGS cells were transfected with NF-κB-luciferase reporter followed by treatment with P. goldsteinii MTS01 (MOI = 200) and H. pylori (MOI = 100) for 6 h. The cell lysates were prepared and subjected to luciferase assays using Dual-Luciferase Reporter Assay System (Promega). Luciferase activity was normalized by co-transfection of β-galactosidase expression vector (Promega), as described previously ( 29 ).…”

Section: Methodsmentioning

confidence: 99%

Gut Commensal Parabacteroides goldsteinii MTS01 Alters Gut Microbiota Composition and Reduces Cholesterol to Mitigate Helicobacter pylori-Induced Pathogenesis

et al. 2022

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Helicobacter pylori infection is closely associated with various gastrointestinal diseases and poses a serious threat to human health owing to its increasing antimicrobial resistance. H. pylori possesses two major virulence factors, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), which are involved in its pathogenesis. Probiotics have recently been used to eradicate H. pylori infection and reduce the adverse effects of antibiotic-based therapies. Parabacteroides goldsteinii MTS01 is a novel next-generation probiotic (NGP) with activities that can alleviate specific diseases by altering the gut microbiota. However, the mechanism by which P. goldsteinii MTS01 exerts its probiotic effects against H. pylori infection remains unclear. Our results showed that administration of P. goldsteinii MTS01 to H. pylori-infected model mice altered the composition of the gut microbiota and significantly reduced serum cholesterol levels, which mitigated H. pylori-induced gastric inflammation. In addition, the pathogenic effects of H. pylori VacA and CagA on gastric epithelial cells were markedly abrogated by treatment with P. goldsteinii MTS01. These results indicate that P. goldsteinii MTS01 can modulate gut microbiota composition and has anti-virulence factor functions, and thus could be developed as a novel functional probiotic for reducing H. pylori-induced pathogenesis.

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Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis

Cited by 8 publications

References 50 publications

Helicobacter pylori cholesterol-α-glucosyltransferase manipulates cholesterol for bacterial adherence to gastric epithelial cells

Helicobacter pylori cholesterol-α-glucosyltransferase manipulates cholesterol for bacterial adherence to gastric epithelial cells

Genetic characteristics and potential pathogenic agents in Campylobacter upsaliensis based on genomic analysis

Gut Commensal Parabacteroides goldsteinii MTS01 Alters Gut Microbiota Composition and Reduces Cholesterol to Mitigate Helicobacter pylori-Induced Pathogenesis

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