Involvement of the actin cytoskeleton and p21rho-family GTPases in the pathogenesis of the human protozoan parasite Entamoeba histolytica

Godbold, Gene D.; Mann, Barbara J.

doi:10.1590/s0100-879x1998000800004

Cited by 17 publications

(12 citation statements)

References 62 publications

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“…The cystic form, being highly resistant, enables the species to be eventually transmitted to other hosts. Central to the pathogenesis of this organism is its ability to directly lyse host cells and cause tissue destruction (Godbold and Mann, 1998).…”

Section: Introductionmentioning

confidence: 99%

Identification, structure, and phylogenetic relationships of a mitogen-activated protein kinase homologue from the parasitic protist Entamoeba histolytica

Ray

Dutta

Banerjee

et al. 2005

Gene

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Section: Introductionmentioning

confidence: 99%

Identification, structure, and phylogenetic relationships of a mitogen-activated protein kinase homologue from the parasitic protist Entamoeba histolytica

Ray

Dutta

Banerjee

et al. 2005

Gene

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“…Cdc42, RhoA and Rac1 are members of the Rho family of small guanosine triphosphatases (GTPases) and are key regulators of actin cytoskeletal remodeling induced by extracellular signals. Moreover, members of this family of GTPases have been implicated in the host cell invasion by many microbes including bacteria and protozoan pathogens (20,22). Whether these GTPases are involved in C. parvum-associated host cytoskeleton remodeling and whether they thus may be required for C. parvum invasion of host cells remain unclear.…”

mentioning

confidence: 99%

Cdc42 and the Actin-Related Protein/Neural Wiskott-Aldrich Syndrome Protein Network Mediate Cellular Invasion by Cryptosporidium parvum

et al. 2004

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Cryptosporidium parvum invasion of epithelial cells involves host cell membrane alterations which require a remodeling of the host cell actin cytoskeleton. In addition, an actin plaque, possibly associated with the dense-band region, forms within the host cytoplasm at the host-parasite interface. Here we show that Cdc42 and RhoA, but not Rac1, members of the Rho family of GTPases, are recruited to the host-parasite interface in an in vitro model of human biliary cryptosporidiosis. Interestingly, activation of Cdc42, but not RhoA, was detected in the infected cells. Neural Wiskott-Aldrich syndrome protein (N-WASP) and p34-Arc, actin-regulating downstream effectors of Cdc42, were also recruited to the host-parasite interface. Whereas cellular expression of a constitutively active mutant of Cdc42 promoted C. parvum invasion, overexpression of a dominant negative mutant of Cdc42, or depletion of Cdc42 mRNA by short interfering RNA-mediated gene silencing, inhibited C. parvum invasion. Expression of the WA fragment of N-WASP to block associated actin polymerization also inhibited C. parvum invasion. Moreover, inhibition of host cell Cdc42 activation by dominant negative mutation inhibited C. parvum-associated actin remodeling, membrane protrusion, and dense-band formation. In contrast, treatment of cells with a Rho inhibitor, exoenzyme C3, or cellular overexpression of dominant negative mutants of RhoA and Rac1 had no effect on C. parvum invasion. These data suggest that C. parvum invasion of target epithelia results from the organism's ability to activate a host cell Cdc42 GTPase signaling pathway to induce host cell actin remodeling at the attachment site.

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“…These results strongly suggest that GSNO impairs the formation of F-actin in NAT. Actin polymerization is essential for the phagocytic and cytopathic activities of E. histolytica (Godbold and Mann, 1998). A comparison between control trophozoites and NAT was carried out using the erythrophagocytosis assay (Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

Identification of S-Nitrosylated (SNO) Proteins in Entamoeba histolytica Adapted to Nitrosative Stress: Insights into the Role of SNO Actin and In vitro Virulence

Trebicz-Geffen

Shahi

Nagaraja

et al. 2017

Front. Cell. Infect. Microbiol.

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We have recently reported that Entamoeba histolytica trophozoites can adapt to toxic levels of the nitric oxide (NO) donor, S-nitrosoglutathione (GSNO). Even if the consequences of this adaptation on the modulation of gene expression in NO-adapted trophozoites (NAT) have been previously explored, insight on S-nitrosylated (SNO) proteins in NAT is missing. Our study aims to fill this knowledge gap by performing a screening of SNO proteins in NAT. Employing SNO resin-assisted capture (RAC), we identified 242 putative SNO proteins with key functions in calcium binding, enzyme modulation, redox homeostasis, and actin cytoskeleton. Of the SNO proteins in NAT, proteins that are associated with actin family cytoskeleton protein are significantly enriched. Here we report that the formation of actin filaments (F-actin) is impaired in NAT. Consequently, the ability of NAT to ingest erythrocytes and their motility and their cytopathic activity are impaired. These phenotypes can be imitated by treating control parasite with cytochalasin D (CytD), a drug that binds to F-actin polymer and prevent polymerization of actin monomers. Removal of GSNO from the culture medium of NAT restored the sensitivity of the parasite to nitrosative stress (NS) and its ability to form F-actin formation and its virulence. These results establish the central role of NO in shaping the virulence of the parasite through its effect on F-actin formation and highlight the impressive ability of this parasite to adapt to NS.

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Involvement of the actin cytoskeleton and p21rho-family GTPases in the pathogenesis of the human protozoan parasite Entamoeba histolytica

Cited by 17 publications

References 62 publications

Identification, structure, and phylogenetic relationships of a mitogen-activated protein kinase homologue from the parasitic protist Entamoeba histolytica

Identification, structure, and phylogenetic relationships of a mitogen-activated protein kinase homologue from the parasitic protist Entamoeba histolytica

Cdc42 and the Actin-Related Protein/Neural Wiskott-Aldrich Syndrome Protein Network Mediate Cellular Invasion by Cryptosporidium parvum

Identification of S-Nitrosylated (SNO) Proteins in Entamoeba histolytica Adapted to Nitrosative Stress: Insights into the Role of SNO Actin and In vitro Virulence

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