Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans ... more Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles fromIxodes scapularisenable tick feeding and promote infection of the mildly virulent rickettsial agentAnaplasma phagocytophilumthrough the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tickDermacentor andersonimitigate microbial spreading caused by the lethal pathogenFrancisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.
Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are pr... more Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite's survival in its host. In order to obtain insight into the mechanism of E. histolytica's adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq). N-acetyl ornithine deacetylase (NAOD) was among the 208 genes that were upregulated in NAT. NAOD catalyzes the deacetylation of N-acetyl-L-ornithine to yield ornithine and acetate. Here, we report that NAOD contributes to the better adaptation of the parasite to nitrosative stress (NS) and that this function does not depend on NAOD catalytic activity. We also demonstrated that glyceraldehyde 3-phosphate dehydrogenase (...
Several members of the genus Entamoeba infect humans including E. histolytica, E. moshkovskii, an... more Several members of the genus Entamoeba infect humans including E. histolytica, E. moshkovskii, and E. dispar. Among these, only E. histolytica is considered pathogenic and is the causal agent of amebiasis. Amebiasis is the second most common cause of death from a parasite worldwide after malaria with considerable morbidity and mortality [1, 2]. Based on the site of infection, the clinical features of amebiasis range from asymptomatic colonization to amebic colitis (dysentery or diarrhea) and invasive extraintestinal amebiasis, which appears most commonly in the form of liver abscesses [2]. According to the World Health Organization, amebiasis occurs worldwide, with approximately 50 million people infected annually, causing close to 100,000 deaths per year. Therefore, it is important to understand the epidemiology, infection, and control of the disease. The aim of this chapter is to provide a current understanding of human amebiasis, which illustrates the parasite biology, mechanism ...
The original version of this Article contained errors in the spelling of the author Sharon Baumel... more The original version of this Article contained errors in the spelling of the author Sharon Baumel-Alterzon, which was incorrectly given as Sharon Alterzon-Baumel. These errors have now been corrected in the PDF and HTML versions of the Article.
Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans ... more Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.
The intestinal protozoan parasite Entamoeba histolytica (Eh) causes amebiasis associated with sev... more The intestinal protozoan parasite Entamoeba histolytica (Eh) causes amebiasis associated with severe diarrhea and/or liver abscess. Eh pathogenesis is multifactorial requiring both parasite virulent molecules and host-induced innate immune responses. Eh-induced host pro-inflammatory responses plays a critical role in disease pathogenesis by causing damage to tissues allowing parasites access to systemic sites. Eh cyclooxygenase (EhCox) derived prostaglandin E 2 stimulates the chemokine IL-8 from mucosal epithelial cells that recruits neutrophils to the site of infection to exacerbate disease. At present, it is not known how EhCox is regulated or whether it affects the expression of other proteins in Eh. In this study, we found that gene silencing of EhCox (EhCoxgs) markedly increased endogenous cysteine protease (CP) protein expression and virulence without altering CP gene transcripts. Live virulent Eh pretreated with arachidonic acid substrate to enhance PGE 2 production or aspirin to inhibit EhCox enzyme activity or addition of exogenous PGE 2 to Eh had no effect on EhCP activity. Increased CP enzyme activity in EhCoxgs was stable and significantly enhanced erythrophagocytosis, cytopathic effects on colonic epithelial cells and elicited pro-inflammatory cytokines in mice colonic loops. Acute infection with EhCoxgs in colonic loops increased inflammation associated with high levels of myeloperoxidase activity. This study has identified EhCox protein as one of the important endogenous regulators of cysteine protease activity. Alterations of CP activity in response to Cox gene silencing may be a negative feedback mechanism in Eh to limit proteolytic activity during colonization that can inadvertently trigger inflammation in the gut.
We have recently reported that Entamoeba histolytica trophozoites can adapt to toxic levels of th... more 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.
Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are pr... more Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite's survival in its host. In order to obtain insight into the mechanism of E. histolytica's adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq). N-acetyl ornithine deacetylase (NAOD) was among the 208 genes that were upregulated in NAT. NAOD catalyzes the deacetylation of N-acetyl-L-ornithine to yield ornithine and acetate. Here, we report that NAOD contributes to the better adaptation of the parasite to nitrosative stress (NS) and that this function does not depend on NAOD catalytic activity. We also demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is detrimental to E. histolytica exposed to NS and that this detrimental effect is neutralized by NAOD or by a catalytically inactive NAOD (mNAOD). These results establish NAOD as a moonlighting protein, and highlight the unexpected role of this metabolic enzyme in the adaptation of the parasite to NS. Intestinal infections are a global medical problem and diarrheal disease is one of the main causes of childhood morbidity and mortality. Entamoeba histolytica is a protozoan parasite and the causal agent of amebiasis, the second most common cause of death from parasitic disease worldwide after malaria (at least 100,000 deaths each year). According to the World Health Organization, amebic dysentery affects 50 million people in India, Southeast Asia, Africa, and Latin America. Since poor sanitary conditions and unsafe hygiene practices exist in many parts of the world, the main mode of transmission of amebiasis is the ingestion of food and/or water that is contaminated with feces and E. histolytica cysts. E. histolytica trophozoites are non-pathogenic commensals in 90% of infected individuals (asymptomatic amebiasis). For unknown reasons, some of these trophozoites can invade the intestinal mucosa, cause dysentery, and migrate to the liver where they produce abscesses (extrain-testinal amebiasis). In the large intestine, E. histolytica is exposed to nanomolar concentrations of nitric oxide (NO) that is produced in intestinal epithelial cells by constitutive NO synthase (NOS) 1 and as an intermediate in denitrification by the intestinal microbiota 2. Although exposure to low NO concentrations is insufficient to kill the parasite 3 , these low concentrations may strengthen its resistance to high NO concentrations. Amebiasis is characterized by acute inflammation of the intestine with the release of cytokines, such as tumor necrosis factor α (TNFα), interleukin 8 (IL-8), interferon gamma (IFN-γ), and interleukin β (IL-1β), and the generation of micromolar concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) from activated cells of the host's immune system (for a recent review see ref. 4). NO in micromolar concentrations is
Entamoeba histolytica is an obligate protozoan parasite of humans, and amebiasis, an infectious d... more Entamoeba histolytica is an obligate protozoan parasite of humans, and amebiasis, an infectious disease which targets the intestine and/or liver, is the second most common cause of human death due to a protozoan after malaria. Although amebiasis is usually asymptomatic, E. histolytica has potent pathogenic potential. During host infection, the parasite is exposed to reactive oxygen species that are produced and released by cells of the innate immune system at the site of infection. The ability of the parasite to survive oxidative stress (OS) is essential for a successful invasion of the host. Although the effects of OS on the regulation of gene expression in E. histolytica and the characterization of some proteins whose function in the parasite's defense against OS have been previously studied, our knowledge of oxidized proteins in E. histolytica is lacking. In order to fill this knowledge gap, we performed a large-scale identification and quantification of the oxidized proteins in oxidatively stressed E. histolytica trophozoites using resin-assisted capture coupled to mass spectrometry. We detected 154 oxidized proteins (OXs) and the functions of some of these proteins were associated with antioxidant activity, maintaining the parasite's cytoskeleton, translation, catalysis, and transport. We also found that oxidation of the Gal/GalNAc impairs its function and contributes to the inhibition of E. histolytica adherence to host cells. We also provide evidence that arginase, an enzyme which converts L-arginine into L-ornithine and urea, is involved in the protection of the parasite against OS. Collectively, these results emphasize the importance of OS as a critical regulator of E. histolytica's functions and indicate a new role for arginase in E. histolytica's resistance to OS.
BACKGROUND: Conventional methods often fail to control the flatheaded borers Capnodis spp., major... more BACKGROUND: Conventional methods often fail to control the flatheaded borers Capnodis spp., major pests of stone fruit trees; the larvae are protected from insecticides and predation because they feed deep in the roots. A potential solution is transgenic trees producing in their roots toxic compounds such as Cry proteins of Bacillus thuringiensis (Bt).
Entamoeba histolytica is a gastrointestinal protozoan parasite that causes amebiasis, a disease w... more Entamoeba histolytica is a gastrointestinal protozoan parasite that causes amebiasis, a disease which has a worldwide distribution with substantial morbidity and mortality. Nitrosative stress, which is generated by innate immune cells, is one of the various environmental challenges that E. histolytica encounters during its life cycle. Although the effects of nitric oxide (NO) on the regulation of gene expression in this parasite have been previously investigated, our knowledge on S-nitrosylated proteins in E.histolytica is lacking. In order to fill this knowledge gap, we performed a large-scale detection of S-nitrosylated (SNO) proteins in E.histolytica trophozoites that were treated with the NO donor, S-nitrosocysteine by resinassisted capture (RAC). We found that proteins involved in glycolysis, gluconeogenesis, translation, protein transport, and adherence to target cells such as the heavy subunit of Gal/GalNac lectin are among the S-nitrosylated proteins that were enriched by SNO-RAC. We also found that the S-nitrosylated cysteine residues in the carbohydrate recognition domain (CRD) of Gal/GalNAc lectin impairs its function and contributes to the inhibition of E.histolytica adherence to host cells. Collectively, these results advance our understanding of the mechanism of reduced E.histolytica adherence to mammalian cells by NO and emphasize the importance of NO as a regulator of key physiological functions in E.histolytica.
LINE-1 (L1) elements are retrotransposons that insert extra copies of themselves throughout the g... more LINE-1 (L1) elements are retrotransposons that insert extra copies of themselves throughout the genome using a "copy and paste" mechanism. L1s have contributed ~20% to total human genome content and are able to influence chromosome integrity and gene expression upon reinsertion. Recent studies show that L1 elements are active and "jumping" during neuronal differentiation. New somatic L1 insertions may generate "genomic plasticity" in neurons by causing variation in genomic DNA sequences and by altering the transcriptome of individual cells. Thus, L1-induced variation may affect neuronal plasticity and behavior. Here, we discuss potential consequences of L1-induced neuronal diversity and propose that a mechanism generating diversity in the brain could broaden the spectrum of behavioral phenotypes that can originate from any single genome.
Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans ... more Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles fromIxodes scapularisenable tick feeding and promote infection of the mildly virulent rickettsial agentAnaplasma phagocytophilumthrough the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tickDermacentor andersonimitigate microbial spreading caused by the lethal pathogenFrancisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.
Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are pr... more Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite's survival in its host. In order to obtain insight into the mechanism of E. histolytica's adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq). N-acetyl ornithine deacetylase (NAOD) was among the 208 genes that were upregulated in NAT. NAOD catalyzes the deacetylation of N-acetyl-L-ornithine to yield ornithine and acetate. Here, we report that NAOD contributes to the better adaptation of the parasite to nitrosative stress (NS) and that this function does not depend on NAOD catalytic activity. We also demonstrated that glyceraldehyde 3-phosphate dehydrogenase (...
Several members of the genus Entamoeba infect humans including E. histolytica, E. moshkovskii, an... more Several members of the genus Entamoeba infect humans including E. histolytica, E. moshkovskii, and E. dispar. Among these, only E. histolytica is considered pathogenic and is the causal agent of amebiasis. Amebiasis is the second most common cause of death from a parasite worldwide after malaria with considerable morbidity and mortality [1, 2]. Based on the site of infection, the clinical features of amebiasis range from asymptomatic colonization to amebic colitis (dysentery or diarrhea) and invasive extraintestinal amebiasis, which appears most commonly in the form of liver abscesses [2]. According to the World Health Organization, amebiasis occurs worldwide, with approximately 50 million people infected annually, causing close to 100,000 deaths per year. Therefore, it is important to understand the epidemiology, infection, and control of the disease. The aim of this chapter is to provide a current understanding of human amebiasis, which illustrates the parasite biology, mechanism ...
The original version of this Article contained errors in the spelling of the author Sharon Baumel... more The original version of this Article contained errors in the spelling of the author Sharon Baumel-Alterzon, which was incorrectly given as Sharon Alterzon-Baumel. These errors have now been corrected in the PDF and HTML versions of the Article.
Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans ... more Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases.
The intestinal protozoan parasite Entamoeba histolytica (Eh) causes amebiasis associated with sev... more The intestinal protozoan parasite Entamoeba histolytica (Eh) causes amebiasis associated with severe diarrhea and/or liver abscess. Eh pathogenesis is multifactorial requiring both parasite virulent molecules and host-induced innate immune responses. Eh-induced host pro-inflammatory responses plays a critical role in disease pathogenesis by causing damage to tissues allowing parasites access to systemic sites. Eh cyclooxygenase (EhCox) derived prostaglandin E 2 stimulates the chemokine IL-8 from mucosal epithelial cells that recruits neutrophils to the site of infection to exacerbate disease. At present, it is not known how EhCox is regulated or whether it affects the expression of other proteins in Eh. In this study, we found that gene silencing of EhCox (EhCoxgs) markedly increased endogenous cysteine protease (CP) protein expression and virulence without altering CP gene transcripts. Live virulent Eh pretreated with arachidonic acid substrate to enhance PGE 2 production or aspirin to inhibit EhCox enzyme activity or addition of exogenous PGE 2 to Eh had no effect on EhCP activity. Increased CP enzyme activity in EhCoxgs was stable and significantly enhanced erythrophagocytosis, cytopathic effects on colonic epithelial cells and elicited pro-inflammatory cytokines in mice colonic loops. Acute infection with EhCoxgs in colonic loops increased inflammation associated with high levels of myeloperoxidase activity. This study has identified EhCox protein as one of the important endogenous regulators of cysteine protease activity. Alterations of CP activity in response to Cox gene silencing may be a negative feedback mechanism in Eh to limit proteolytic activity during colonization that can inadvertently trigger inflammation in the gut.
We have recently reported that Entamoeba histolytica trophozoites can adapt to toxic levels of th... more 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.
Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are pr... more Adaptation of the Entamoeba histolytica parasite to toxic levels of nitric oxide (NO) that are produced by phagocytes may be essential for the establishment of chronic amebiasis and the parasite's survival in its host. In order to obtain insight into the mechanism of E. histolytica's adaptation to NO, E. histolytica trophozoites were progressively adapted to increasing concentrations of the NO donor drug, S-nitrosoglutathione (GSNO) up to a concentration of 110 μM. The transcriptome of NO adapted trophozoites (NAT) was investigated by RNA sequencing (RNA-seq). N-acetyl ornithine deacetylase (NAOD) was among the 208 genes that were upregulated in NAT. NAOD catalyzes the deacetylation of N-acetyl-L-ornithine to yield ornithine and acetate. Here, we report that NAOD contributes to the better adaptation of the parasite to nitrosative stress (NS) and that this function does not depend on NAOD catalytic activity. We also demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is detrimental to E. histolytica exposed to NS and that this detrimental effect is neutralized by NAOD or by a catalytically inactive NAOD (mNAOD). These results establish NAOD as a moonlighting protein, and highlight the unexpected role of this metabolic enzyme in the adaptation of the parasite to NS. Intestinal infections are a global medical problem and diarrheal disease is one of the main causes of childhood morbidity and mortality. Entamoeba histolytica is a protozoan parasite and the causal agent of amebiasis, the second most common cause of death from parasitic disease worldwide after malaria (at least 100,000 deaths each year). According to the World Health Organization, amebic dysentery affects 50 million people in India, Southeast Asia, Africa, and Latin America. Since poor sanitary conditions and unsafe hygiene practices exist in many parts of the world, the main mode of transmission of amebiasis is the ingestion of food and/or water that is contaminated with feces and E. histolytica cysts. E. histolytica trophozoites are non-pathogenic commensals in 90% of infected individuals (asymptomatic amebiasis). For unknown reasons, some of these trophozoites can invade the intestinal mucosa, cause dysentery, and migrate to the liver where they produce abscesses (extrain-testinal amebiasis). In the large intestine, E. histolytica is exposed to nanomolar concentrations of nitric oxide (NO) that is produced in intestinal epithelial cells by constitutive NO synthase (NOS) 1 and as an intermediate in denitrification by the intestinal microbiota 2. Although exposure to low NO concentrations is insufficient to kill the parasite 3 , these low concentrations may strengthen its resistance to high NO concentrations. Amebiasis is characterized by acute inflammation of the intestine with the release of cytokines, such as tumor necrosis factor α (TNFα), interleukin 8 (IL-8), interferon gamma (IFN-γ), and interleukin β (IL-1β), and the generation of micromolar concentrations of reactive oxygen species (ROS) and reactive nitrogen species (RNS) from activated cells of the host's immune system (for a recent review see ref. 4). NO in micromolar concentrations is
Entamoeba histolytica is an obligate protozoan parasite of humans, and amebiasis, an infectious d... more Entamoeba histolytica is an obligate protozoan parasite of humans, and amebiasis, an infectious disease which targets the intestine and/or liver, is the second most common cause of human death due to a protozoan after malaria. Although amebiasis is usually asymptomatic, E. histolytica has potent pathogenic potential. During host infection, the parasite is exposed to reactive oxygen species that are produced and released by cells of the innate immune system at the site of infection. The ability of the parasite to survive oxidative stress (OS) is essential for a successful invasion of the host. Although the effects of OS on the regulation of gene expression in E. histolytica and the characterization of some proteins whose function in the parasite's defense against OS have been previously studied, our knowledge of oxidized proteins in E. histolytica is lacking. In order to fill this knowledge gap, we performed a large-scale identification and quantification of the oxidized proteins in oxidatively stressed E. histolytica trophozoites using resin-assisted capture coupled to mass spectrometry. We detected 154 oxidized proteins (OXs) and the functions of some of these proteins were associated with antioxidant activity, maintaining the parasite's cytoskeleton, translation, catalysis, and transport. We also found that oxidation of the Gal/GalNAc impairs its function and contributes to the inhibition of E. histolytica adherence to host cells. We also provide evidence that arginase, an enzyme which converts L-arginine into L-ornithine and urea, is involved in the protection of the parasite against OS. Collectively, these results emphasize the importance of OS as a critical regulator of E. histolytica's functions and indicate a new role for arginase in E. histolytica's resistance to OS.
BACKGROUND: Conventional methods often fail to control the flatheaded borers Capnodis spp., major... more BACKGROUND: Conventional methods often fail to control the flatheaded borers Capnodis spp., major pests of stone fruit trees; the larvae are protected from insecticides and predation because they feed deep in the roots. A potential solution is transgenic trees producing in their roots toxic compounds such as Cry proteins of Bacillus thuringiensis (Bt).
Entamoeba histolytica is a gastrointestinal protozoan parasite that causes amebiasis, a disease w... more Entamoeba histolytica is a gastrointestinal protozoan parasite that causes amebiasis, a disease which has a worldwide distribution with substantial morbidity and mortality. Nitrosative stress, which is generated by innate immune cells, is one of the various environmental challenges that E. histolytica encounters during its life cycle. Although the effects of nitric oxide (NO) on the regulation of gene expression in this parasite have been previously investigated, our knowledge on S-nitrosylated proteins in E.histolytica is lacking. In order to fill this knowledge gap, we performed a large-scale detection of S-nitrosylated (SNO) proteins in E.histolytica trophozoites that were treated with the NO donor, S-nitrosocysteine by resinassisted capture (RAC). We found that proteins involved in glycolysis, gluconeogenesis, translation, protein transport, and adherence to target cells such as the heavy subunit of Gal/GalNac lectin are among the S-nitrosylated proteins that were enriched by SNO-RAC. We also found that the S-nitrosylated cysteine residues in the carbohydrate recognition domain (CRD) of Gal/GalNAc lectin impairs its function and contributes to the inhibition of E.histolytica adherence to host cells. Collectively, these results advance our understanding of the mechanism of reduced E.histolytica adherence to mammalian cells by NO and emphasize the importance of NO as a regulator of key physiological functions in E.histolytica.
LINE-1 (L1) elements are retrotransposons that insert extra copies of themselves throughout the g... more LINE-1 (L1) elements are retrotransposons that insert extra copies of themselves throughout the genome using a "copy and paste" mechanism. L1s have contributed ~20% to total human genome content and are able to influence chromosome integrity and gene expression upon reinsertion. Recent studies show that L1 elements are active and "jumping" during neuronal differentiation. New somatic L1 insertions may generate "genomic plasticity" in neurons by causing variation in genomic DNA sequences and by altering the transcriptome of individual cells. Thus, L1-induced variation may affect neuronal plasticity and behavior. Here, we discuss potential consequences of L1-induced neuronal diversity and propose that a mechanism generating diversity in the brain could broaden the spectrum of behavioral phenotypes that can originate from any single genome.
Uploads
Papers by Preeti Shahi