Regulatory Effects of Black Rice Extract on <i>Helicobacter pylori</i> Infection‐Induced Apoptosis

Kim, Sa-Hyun; Lee, Min Ho; Park, Min; Woo, Hyun Jun; Kim, Yoon Suk; Tharmalingam, Nagendran; Seo, Woo-Duck; Kim, Jong-Bae

doi:10.1002/mnfr.201700586

Cited by 19 publications

(16 citation statements)

References 42 publications

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“…The system has been merely studied in H . pylori thus far 30–33 , although it is presumably the major protein translocation system in this bacterium 34,35 . Moreover, the Sec translocon is involved in translocation of vacuolating cytotoxin A (VacA) – one other major H .…”

Section: Discussionmentioning

confidence: 99%

Establishment of serine protease htrA mutants in Helicobacter pylori is associated with secA mutations

Zawilak-Pawlik

Zarzecka

Żyła-Uklejewicz

et al. 2019

Sci Rep

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Helicobacter pylori plays an essential role in the pathogenesis of gastritis, peptic ulcer disease, and gastric cancer. The serine protease HtrA, an important secreted virulence factor, disrupts the gastric epithelium, which enables H . pylori to transmigrate across the epithelium and inject the oncogenic CagA protein into host cells. The function of periplasmic HtrA for the H . pylori cell is unknown, mainly due to unavailability of the htrA mutants. In fact, htrA has been described as an essential gene in this bacterium. We have screened 100 worldwide H . pylori isolates and show that only in the N6 strain it was possible to delete htrA or mutate the htrA gene to produce proteolytically inactive HtrA. We have sequenced the wild-type and mutant chromosomes and we found that inactivation of htrA is associated with mutations in SecA – a component of the Sec translocon apparatus used to translocate proteins from the cytoplasm into the periplasm. The cooperation of SecA and HtrA has been already suggested in Streptococcus pneumonia , in which these two proteins co-localize. Hence, our results pinpointing a potential functional relationship between HtrA and the Sec translocon in H . pylori possibly indicate for the more general mechanism responsible to maintain bacterial periplasmic homeostasis.

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Section: Discussionmentioning

confidence: 99%

Establishment of serine protease htrA mutants in Helicobacter pylori is associated with secA mutations

Zawilak-Pawlik

Zarzecka

Żyła-Uklejewicz

et al. 2019

Sci Rep

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“…Mammalian cell lines HepG2 (hepatic cells), A549 (epithelial cells), and MKN-28 (gastric cells) were used to measure the anti-proliferative properties of test compounds, as described elsewhere [ 28 ]. Cells were grown in Dulbecco’s Modified Eagle Medium (DMEM) (Gibco, Waltham, MA, USA) supplemented with 10% Fetal Bovine Serum (FBS) (Gibco, Waltham, MA, USA) and 1% penicillin/streptomycin (Gibco, Waltham, MA, USA) and maintained at 37 °C in 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Characterization of Five Novel Anti-MRSA Compounds Identified Using a Whole-Animal Caenorhabditis elegans/Galleria mellonella Sequential-Screening Approach

et al. 2020

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There is a significant need to combat the growing challenge of antibacterial drug resistance. We have previously developed a whole-animal dual-screening platform that first used the nematode Caenorhabditis elegans, to identify low-toxicity antibacterial hits in a high-throughput format. The hits were then evaluated in the wax moth caterpillar Galleria mellonella infection model to confirm efficacy and low toxicity at a whole animal level. This multi-host approach is a powerful tool for revealing compounds that show antibacterial effects and relatively low toxicity at the whole organism level. This paper reports the use of the multi-host approach to identify and validate five new anti-staphylococcal compounds: (1) 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol(PPT), (2) (1S,2S)-2-[2-[[3-(1H-benzimidazol-2-yl)propyl]methylamino]ethyl]-6-fluoro-1,2,3,4-tetrahydro-1-(1-methylethyl)-2-naphthalenyl cyclopropanecarboxylate dihydrochloride(NNC), (3) 4,5,6,7-tetrabromobenzotriazole (TBB), (4) 3-[2-[2-chloro-4-[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl] benzoic acid(GW4064), and (5) N-(cyclopropylmethoxy)-3,4,5-trifluoro-2-[(4-iodo-2-methylphenyl)amino] benzamide(PD198306). The compounds reduced the severity of methicillin-resistant Staphylococcus aureus (MRSA, strain MW2) infections in both C. elegans and G. mellonella and showed minimal inhibitory concentrations (MICs) in the range of 2–8 µg/mL. Compounds NNC, PPT, and TBB permeabilized MRSA-MW2 cells to SYTOX green, suggesting that they target bacterial membranes. Compound TBB showed synergistic activity with doxycycline and oxacillin against MRSA-MW2, and compounds PPT, NNC, GW4064, and PD198306 synergized with doxycycline, polymyxin-B, gentamicin, and erythromycin, respectively. The study demonstrates the utility of the multi-host approach with follow-up hit characterization for prioritizing anti-MRSA compounds for further evaluation.

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“…It has been reported that C3G can potentially inhibit human colon cancer cell proliferation through promoting apoptosis and suppressing angiogenesis [106,107]. But in other normal cases, C3G showed the protective effects on gastrointestinal cells, as well as endothelial cells, and obviously inhibited apoptosis by regulating apoptosis associated proteins, such as reducing the cytoplasmatic levels in Bax [108] and inhibiting the expression of caspase-8 [109], caspase-9 [108], and caspase-3 [108,109] to attenuate gastrointestinal damage. The impacts of C3G-Ms on apoptosis are similar to C3G, and multiple studies have suggested that PCA [35,36,100] and FA [110,111] may act against apoptosis in various models, although other studies revealed that C3G-Ms (PCA, FA) might promote apoptosis of colorectal adenocarcinoma cells [112].…”

Section: Anti-apoptosismentioning

confidence: 99%

The Effects and Mechanisms of Cyanidin-3-Glucoside and Its Phenolic Metabolites in Maintaining Intestinal Integrity

et al. 2019

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Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin and possesses antioxidant and anti-inflammatory properties. The catabolism of C3G in the gastrointestinal tract could produce bioactive phenolic metabolites, such as protocatechuic acid, phloroglucinaldehyde, vanillic acid, and ferulic acid, which enhance C3G bioavailability and contribute to both mucosal barrier and microbiota. To get an overview of the function and mechanisms of C3G and its phenolic metabolites, we review the accumulated data of the absorption and catabolism of C3G in the gastrointestine, and attempt to give crosstalk between the phenolic metabolites, gut microbiota, and mucosal innate immune signaling pathways.

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Regulatory Effects of Black Rice Extract on Helicobacter pylori Infection‐Induced Apoptosis

Cited by 19 publications

References 42 publications

Establishment of serine protease htrA mutants in Helicobacter pylori is associated with secA mutations

Establishment of serine protease htrA mutants in Helicobacter pylori is associated with secA mutations

Characterization of Five Novel Anti-MRSA Compounds Identified Using a Whole-Animal Caenorhabditis elegans/Galleria mellonella Sequential-Screening Approach

The Effects and Mechanisms of Cyanidin-3-Glucoside and Its Phenolic Metabolites in Maintaining Intestinal Integrity

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