Cryptosporidium parvum alters glucose transport mechanisms in infected enterocytes

Delling, Cora; Daugschies, Arwid; Bangoura, Berit; Dengler, Franziska

doi:10.1007/s00436-019-06471-y

Cited by 10 publications

(9 citation statements)

References 47 publications

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“…Recent research showed that C . parvum could interfere with host glucose transporters (GLUT) 1/2 and Na + -coupled glucose transporter (SGLT) 1 expression, and a significantly higher intracellular glucose level was observed in infected cells, which would point to an adaptation of the host cells’ glucose uptake after infection [ 89 ]. Based on this, PGAM1 might be a new target for C .…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomics reveals Cryptosporidium parvum manipulation of the host cell molecular expression and immune response

Liu

Jiang

et al. 2021

PLoS Negl Trop Dis

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Cryptosporidium is a life-threating protozoan parasite belonging to the phylum Apicomplexa, which mainly causes gastroenteritis in a variety of vertebrate hosts. Currently, there is a re-emergence of Cryptosporidium infection; however, no fully effective drug or vaccine is available to treat Cryptosporidiosis. In the present study, to better understand the detailed interaction between the host and Cryptosporidium parvum, a large-scale label-free proteomics study was conducted to characterize the changes to the proteome induced by C. parvum infection. Among 4406 proteins identified, 121 proteins were identified as differentially abundant (> 1.5-fold cutoff, P < 0.05) in C. parvum infected HCT-8 cells compared with uninfected cells. Among them, 67 proteins were upregulated, and 54 proteins were downregulated at 36 h post infection. Analysis of the differentially abundant proteins revealed an interferon-centered immune response of the host cells against C. parvum infection and extensive inhibition of metabolism-related enzymes in the host cells caused by infection. Several proteins were further verified using quantitative real-time reverse transcription polymerase chain reaction and western blotting. This systematic analysis of the proteomics of C. parvum-infected HCT-8 cells identified a wide range of functional proteins that participate in host anti-parasite immunity or act as potential targets during infection, providing new insights into the molecular mechanism of C. parvum infection.

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Section: Discussionmentioning

confidence: 99%

Comparative proteomics reveals Cryptosporidium parvum manipulation of the host cell molecular expression and immune response

Liu

Jiang

et al. 2021

PLoS Negl Trop Dis

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“…Alternatively, CLAG3, RhopH2, and RhopH3 may activate an endogenous host channel [43]. Similarly, but using a different mechanism, Cryptosporidium enhances the capability of parasitized enterocytes to internalize glucose by upregulating transcription of the host gene GLUT1, although the authors did not address GLUT1 expression at the protein level [44].…”

Section: Scavenging Nutrients Across a Physical Barrier-the Pvmmentioning

confidence: 99%

An Uninvited Seat at the Dinner Table: How Apicomplexan Parasites Scavenge Nutrients from the Host

et al. 2021

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Obligate intracellular parasites have evolved a remarkable assortment of strategies to scavenge nutrients from the host cells they parasitize. Most apicomplexans form a parasitophorous vacuole (PV) within the invaded cell, a replicative niche within which they survive and multiply. As well as providing a physical barrier against host cell defense mechanisms, the PV membrane (PVM) is also an important site of nutrient uptake that is essential for the parasites to sustain their metabolism. This means nutrients in the extracellular milieu are separated from parasite metabolic machinery by three different membranes, the host plasma membrane, the PVM, and the parasite plasma membrane (PPM). In order to facilitate nutrient transport from the extracellular environment into the parasite itself, transporters on the host cell membrane of invaded cells can be modified by secreted and exported parasite proteins to maximize uptake of key substrates to meet their metabolic demand. To overcome the second barrier, the PVM, apicomplexan parasites secrete proteins contained in the dense granules that remodel the vacuole and make the membrane permissive to important nutrients. This bulk flow of host nutrients is followed by a more selective uptake of substrates at the PPM that is operated by specific transporters of this third barrier. In this review, we recapitulate and compare the strategies developed by Apicomplexa to scavenge nutrients from their hosts, with particular emphasis on transporters at the parasite plasma membrane and vacuolar solute transporters on the parasite intracellular digestive organelle.

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“…The formation of this F-actin pedestal at the site of infection has been directly linked to the actin-associated signaling pathways of the neural Wiskott-Aldrich syndrome protein (N-WASP) and the Arp2/3 complex ( 20 ). The membrane protrusions encapsulating Cryptosporidium during invasion are additionally dependent on localized volume increases mediated by glucose and water influxes ( 21 , 22 ). The recruitment of Na + /glucose cotransporter (SGLT1) and aquaporin 1 (AQP1) to the site of infection contributes to this actin-dependent cellular invasion.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase C-α Is a Gatekeeper of Cryptosporidium Sporozoite Adherence and Invasion

2022

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Cryptosporidium infection is a leading cause of diarrhea-associated morbidity and mortality in young children, globally. Single nucleotide polymorphisms (SNP) in the human protein kinase C alpha ( PRKCA ) gene region have been associated with susceptibility to cryptosporidiosis. Here, we examined the role of protein kinase C-α (PKCα) activity in human HCT-8 intestinal epithelial cells during infection with Cryptosporidium parvum sporozoites. To delineate the role of PKCα in infection, we developed a fluorescence-based imaging assay to differentiate adherent from intracellular parasite. We tested pharmacologic agonists and antagonists of PKCα and measured the effect on C. parvum sporozoite adherence and invasion of HCT-8 cells. We demonstrated both PKCα agonists and antagonists significantly alter parasite adherence and invasion in vitro . We found HCT-8 cell PKCα is activated by C. parvum infection. Our findings suggest intestinal epithelial cell PKCα as a potential host-directed therapeutic target for cryptosporidiosis and implicate PKCα activity as a mediator of parasite adherence and invasion.

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Cryptosporidium parvum alters glucose transport mechanisms in infected enterocytes

Cited by 10 publications

References 47 publications

Comparative proteomics reveals Cryptosporidium parvum manipulation of the host cell molecular expression and immune response

Comparative proteomics reveals Cryptosporidium parvum manipulation of the host cell molecular expression and immune response

An Uninvited Seat at the Dinner Table: How Apicomplexan Parasites Scavenge Nutrients from the Host

Protein Kinase C-α Is a Gatekeeper of Cryptosporidium Sporozoite Adherence and Invasion

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