Discovery of novel PC‐PLC activity inhibitors

Zhao, Yi; Su, Le; Li, Kunlun; Zhao, Bao‐Xiang

doi:10.1111/cbdd.13606

Cited by 6 publications

(4 citation statements)

References 28 publications

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“…PI‐PLC and phosphatidylcholine‐specific phospholipase C exhibit hemolytic activity. PI‐PLC is a recognized virulence factor that contributes to infective diseases in mammals, leading to apoptosis, proliferation, differentiation, and metastasis (Zhao et al., 2020). Further, HlyI (or cereolysin O) belongs to the cholesterol‐dependent cytolysin family of proteins that are able to bind to cholesterol on the cell surface and form transmembrane pores during infection (Beecher et al., 2000).…”

Section: Bacillus Cereus Pathogenic Toolkit: Toxins and Virulence Factorsmentioning

confidence: 99%

Bacillus cereus food intoxication and toxicoinfection

Jovanović

Ornelis

Madder

et al. 2021

Comp Rev Food Sci Food Safe

126

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Bacillus cereus is one of the leading etiological agents of toxin‐induced foodborne diseases. Its omnipresence in different environments, spore formation, and its ability to adapt to varying conditions and produce harmful toxins make this pathogen a health hazard that should not be underestimated. Food poisoning by B. cereus can manifest itself as an emetic or diarrheal syndrome. The former is caused by the release of the potent peptide toxin cereulide, whereas the latter is the result of proteinaceous enterotoxins (e.g., hemolysin BL, nonhemolytic enterotoxin, and cytotoxin K). The final harmful effect is not only toxin and strain dependent, but is also affected by the stress responses, accessory virulence factors, and phenotypic properties under extrinsic, intrinsic, and explicit food conditions and host‐related environment. Infamous portrait of B. cereus as a foodborne pathogen, as well as a causative agent of nongastrointestinal infections and even nosocomial complications, has inspired vast volumes of multidisciplinary research in food and clinical domains. As a result, extensive original data became available asking for a new, both broad and deep, multifaceted look into the current state‐of‐the art regarding the role of B. cereus in food safety. In this review, we first provide an overview of the latest knowledge on B. cereus toxins and accessory virulence factors. Second, we describe the novel taxonomy and some of the most pertinent phenotypic characteristics of B. cereus related to food safety. We link these aspects to toxin production, overall pathogenesis, and interactions with its human host. Then we reflect on the prevalence of different toxinotypes in foods opening the scene for epidemiological aspects of B. cereus foodborne diseases and methods available to prevent food poisoning including overview of the different available methods to detect B. cereus and its toxins.

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Section: Bacillus Cereus Pathogenic Toolkit: Toxins and Virulence Factorsmentioning

confidence: 99%

Bacillus cereus food intoxication and toxicoinfection

Jovanović

Ornelis

Madder

et al. 2021

Comp Rev Food Sci Food Safe

126

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“…To test whether the increase in DAG, PA and PG upon CAY94 treatment comes from PC, one should specifically block PC-PLC activity in combination with CAY94. Although the PC-PLC activity has been known for years, the mammalian PC-PLC has not been purified and the gene sequence has not yet been resolved [57]. The only commercially available pharmacological inhibitor of PC-PLC (D609) has several off-target effects [58], including inhibition of sphingomyelin synthase at similar concentrations as used to inhibit PC-PLC [59], thus at this point, we are not able to test our hypothesis.…”

Section: Discussionmentioning

confidence: 93%

Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus

Lingelem

Kavaliauskiene

Halsne

et al. 2020

Cell. Mol. Life Sci.

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The membrane lipids diacylglycerol (DAG) and phosphatidic acid (PA) are important second messengers that can regulate membrane transport by recruiting proteins to the membrane and by altering biophysical membrane properties. DAG and PA are involved in the transport from the Golgi apparatus to endosomes, and we have here investigated whether changes in these lipids might be important for regulation of transport to the Golgi using the protein toxin ricin. Modulation of DAG and PA levels using DAG kinase (DGK) and phospholipase D (PLD) inhibitors gave a strong increase in retrograde ricin transport, but had little impact on ricin recycling or degradation. Inhibitor treatment strongly affected the endosome morphology, increasing endosomal tubulation and size. Furthermore, ricin was present in these tubular structures together with proteins known to regulate retrograde transport. Using siRNA to knock down different isoforms of PLD and DGK, we found that several isoforms of PLD and DGK are involved in regulating ricin transport to the Golgi. Finally, by performing lipidomic analysis we found that the DGK inhibitor gave a weak, but expected, increase in DAG levels, while the PLD inhibitor gave a strong and unexpected increase in DAG levels, showing that it is important to perform lipidomic analysis when using inhibitors of lipid metabolism.

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“…The process of LysoPC passing through phosphatidylcholine to generate DAG as well as PE to generate DAG was activated. PLC hydrolyzes phosphatidylcholine and PE to generate DAG, which is required for membrane phospholipid and storage lipid production [61,62]. Together, phosphatidylcholine shifted acrylamide -induced phosphatidylcholine to LysoPC production to storage from LysoPC to DAG by downregulating LCAT and PEMT, and upregulating PLCB1.…”

Section: Gene Expression Involved With Differential Metabolitesmentioning

confidence: 99%

Phosphatidylcholine protects against the hepatotoxicity of acrylamide via maintaining metabolic homeostasis of glutathione and glycerophospholipid

Li,

Jia,

Zhang

et al. 2024

Food Science and Human Wellness

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Discovery of novel PC‐PLC activity inhibitors

Cited by 6 publications

References 28 publications

Bacillus cereus food intoxication and toxicoinfection

Bacillus cereus food intoxication and toxicoinfection

Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus

Phosphatidylcholine protects against the hepatotoxicity of acrylamide via maintaining metabolic homeostasis of glutathione and glycerophospholipid

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