Involvement of Cholesterol in
            <i>Campylobacter jejuni</i>
            Cytolethal Distending Toxin-Induced Pathogenesis

Lai, Cheng Kuo; Su, Jing Chi; Lin, Yu Hsin; Chang, Chia Shuo; Feng, Chun; Lin, Hwai Jeng; Lin, Chun Jung; Tseng, Guan Chin; Liu, Hsin Ho; Hsieh, Jer Tsong; Su, Hong; Lai, Chih Ho

doi:10.2217/fmb.14.119

Cited by 15 publications

(13 citation statements)

References 57 publications

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“…It should be pointed out that in a more recent study in which Cdts from different microbial species were studied simultaneously, toxin-host interactions were shown not to depend upon fucosylated structures as well as N- and O-glycans (Eshraghi et al, 2010). These authors did, however, observe that several Cdts, including toxin prepared from A. actinomycetemcomitans, C. jejuni , and H. ducreyi , utilized membrane cholesterol; these results corroborated the findings of several other investigators (Guerra et al, 2005; Boesze-Battaglia et al, 2009; Zhou et al, 2012; Lai et al, 2013, 2015). …”

Section: Cdt Subunit Structure and Functionsupporting

confidence: 78%

The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin

Scuron

Boesze‐Battaglia

Dlakić

et al. 2016

Front. Cell. Infect. Microbiol.

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This review summarizes the current status and recent advances in our understanding of the role that the cytolethal distending toxin (Cdt) plays as a virulence factor in promoting disease by toxin-producing pathogens. A major focus of this review is on the relationship between structure and function of the individual subunits that comprise the AB2 Cdt holotoxin. In particular, we concentrate on the molecular mechanisms that characterize this toxin and which account for the ability of Cdt to intoxicate multiple cell types by utilizing a ubiquitous binding partner on the cell membrane. Furthermore, we propose a paradigm shift for the molecular mode of action by which the active Cdt subunit, CdtB, is able to block a key signaling cascade and thereby lead to outcomes based upon programming and the role of the phosphatidylinositol 3-kinase (PI-3K) in a variety of cells. Based upon the collective Cdt literature, we now propose that Cdt is a unique and potent virulence factor capable of acting as a tri-perditious toxin that impairs host defenses by: (1) disrupting epithelial barriers; (2) suppressing acquired immunity; (3) promoting pro-inflammatory responses. Thus, Cdt plays a key role in facilitating the early stages of infection and the later stages of disease progression by contributing to persistence and impairing host elimination.

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Section: Cdt Subunit Structure and Functionsupporting

confidence: 78%

The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin

Scuron

Boesze‐Battaglia

Dlakić

et al. 2016

Front. Cell. Infect. Microbiol.

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“…In particular, cholesterol plays a crucial role in H. pylori cell invasion and virulence (Lai et al, 2013). Depletion of cellular cholesterol not only attenuates H. pylori -induced pathogenesis (Hutton et al, 2010; Lai et al, 2011) but also promotes autophagy (Cheng et al, 2006), which has been shown to contribute to immune defense against invading pathogens (Levine et al, 2011; Deretic et al, 2013; Lai et al, 2015). Statins, inhibitors of HMG-CoA reductase that are widely prescribed for lowering serum cholesterol, have also been employed to reduce the risk of certain bacterial infections (Chow et al, 2010; Nseir et al, 2010; Boyd et al, 2012; Motzkus-Feagans et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Statin Decreases Helicobacter pylori Burden in Macrophages by Promoting Autophagy

Liao

Huang

Wang

et al. 2017

Front. Cell. Infect. Microbiol.

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Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, have been found to provide protective effects against several bacterial infectious diseases. Although the use of statins has been shown to enhance antimicrobial treated Helicobacter pylori eradication and reduce H. pylori-mediated inflammation, the mechanisms underlying these effects remain unclear. In this study, in vitro and ex vivo macrophage models were established to investigate the molecular pathways involved in statin-mediated inhibition of H. pylori-induced inflammation. Our study showed that statin treatment resulted in a dose-dependent decrease in intracellular H. pylori burden in both RAW264.7 macrophage cells and murine peritoneal exudate macrophages (PEMs). Furthermore, statin yielded enhanced early endosome maturation and subsequent activation of the autophagy pathway, which promotes lysosomal fusion resulting in degradation of sequestered bacteria, and in turn attenuates interleukin (IL)-1β production. These results indicate that statin not only reduces cellular cholesterol but also decreases the H. pylori burden in macrophages by promoting autophagy, consequently alleviating H. pylori-induced inflammation.

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“…Tissue specimens from mice were formalin-fixed then subjected to IHC staining as described previously [27,34]. Briefly, the tissue sections were de-waxed and rehydrated.…”

Section: Methodsmentioning

confidence: 99%

Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems

et al. 2017

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Resveratrol (RV, 3,4ʹ,5-trihydroxystilbene) is naturally produced by a wide variety of plants including grapes and peanuts (Arachis hypogaea). However, the yield of RV from peanut stem and its potential radiosensitizing effects in prostate cancer (PCa) have not been well investigated. In this study, we characterized RV in peanut stem extract (PSE) for the first time and showed that both RV and PSE dose-dependently induced cell death in DOC-2/DAB2 interactive protein (DAB2IP)-deficient PCa cells with the radioresistant phenotype. Furthermore, the combination of radiation with either RV or PSE induced the death of radioresistant PCa cells through delayed repair of radiation-induced DNA double-strand break (DSB) and prolonged G2/M arrest, which induced apoptosis. The administration of RV and PSE effectively enhanced radiation therapy in the shDAB2IP PCa xenograft mouse model. These results demonstrate the promising synergistic effect of RV and PSE combined with radiation in the treatment of radioresistant PCa.

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Involvement of Cholesterol in Campylobacter jejuni Cytolethal Distending Toxin-Induced Pathogenesis

Abstract: Our findings demonstrate a molecular link between Campylobacter jejuni CDT and cholesterol, which is crucial to facilitate CDT-induced pathogenesis in hosts.

Cited by 15 publications

References 57 publications

The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin

The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin

Statin Decreases Helicobacter pylori Burden in Macrophages by Promoting Autophagy

Sensitization of Radioresistant Prostate Cancer Cells by Resveratrol Isolated from Arachis hypogaea Stems

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