scholarly journals Metamorphoses of malaria: the role of autophagy in parasite differentiation

2011 ◽  
Vol 51 ◽  
pp. 127-136 ◽  
Author(s):  
Isabelle Coppens
Keyword(s):  
Life Cycle ◽  
Complex Life Cycle ◽  
Mammalian Host ◽  
Protozoan Parasites ◽  
Membrane Complex ◽  
Autophagic Process ◽  
Inner Membrane Complex ◽  
Form Development ◽  
High Degree

Several protozoan parasites undergo a complex life cycle that alternates between an invertebrate vector and a vertebrate host. Adaptations to these different environments by the parasites are achieved by drastic changes in their morphology and metabolism. The malaria parasites must be transmitted to a mammal from a mosquito as part of their life cycle. Upon entering the mammalian host, extracellular malaria sporozoites reach the liver and invade hepatocytes, wherein they meet the challenge of becoming replication-competent schizonts. During the process of conversion, the sporozoite selectively discards organelles that are unnecessary for the parasite growth in liver cells. Among the organelles that are cleared from the sporozoite are the micronemes, abundant secretory vesicles that facilitate the adhesion of the parasite to hepatocytes. Organelles specialized in sporozoite motility and structure, such as the inner membrane complex (a major component of the motile parasite's cytoskeleton), are also eliminated from converting parasites. The high degree of sophistication of the metamorphosis that occurs at the onset of the liver-form development cascade suggests that the observed changes must be multifactorial. Among the mechanisms implicated in the elimination of sporozoite organelles, the degradative process called autophagy contributes to the remodelling of the parasite interior and the production of replicative liver forms. In a broader context, the importance of the role played by autophagy during the differentiation of protozoan parasites that cycle between insects and vertebrates is nowadays clearly emerging. An exciting prospect derived from these observations is that the parasite proteins involved in the autophagic process may represent new targets for drug development.

scholarly journals Glutamine Analogues Impair Cell Proliferation, the Intracellular Cycle and Metacyclogenesis in Trypanosoma cruzi

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1628
Author(s):  
Rodolpho Ornitz Oliveira Souza ◽  
Marcell Crispim ◽  
Ariel Mariano Silber ◽  
Flávia Silva Damasceno
Keyword(s):  
Cell Proliferation ◽  
Life Cycle ◽  
Trypanosoma Cruzi ◽  
Host Cells ◽  
Glutamine Metabolism ◽  
Complex Life Cycle ◽  
Mammalian Host ◽  
Developmental Cycle ◽  
Parasite Life Cycle

Trypanosoma cruzi is the aetiologic agent of Chagas disease, which affects people in the Americas and worldwide. The parasite has a complex life cycle that alternates among mammalian hosts and insect vectors. During its life cycle, T. cruzi passes through different environments and faces nutrient shortages. It has been established that amino acids, such as proline, histidine, alanine, and glutamate, are crucial to T. cruzi survival. Recently, we described that T. cruzi can biosynthesize glutamine from glutamate and/or obtain it from the extracellular environment, and the role of glutamine in energetic metabolism and metacyclogenesis was demonstrated. In this study, we analysed the effect of glutamine analogues on the parasite life cycle. Here, we show that glutamine analogues impair cell proliferation, the developmental cycle during the infection of mammalian host cells and metacyclogenesis. Taken together, these results show that glutamine is an important metabolite for T. cruzi survival and suggest that glutamine analogues can be used as scaffolds for the development of new trypanocidal drugs. These data also reinforce the supposition that glutamine metabolism is an unexplored possible therapeutic target.

scholarly journals Role of two metacaspases in development and pathogenicity of the Rice Blast fungus, Magnaporthe oryzae

2020 ◽  
Author(s):  
Jessie Fernandez ◽  
Victor Lopez ◽  
Lisa Kinch ◽  
Mariel A. Pfeifer ◽  
Hillery Gray ◽  
...  
Keyword(s):  
Cell Death ◽  
Food Security ◽  
Life Cycle ◽  
Magnaporthe Oryzae ◽  
Rice Blast ◽  
Rice Blast Disease ◽  
Blast Disease ◽  
Complex Life Cycle ◽  
Insight Into

ABSTRACTRice blast disease caused by Magnaporthe oryzae is a devastating disease of cultivated rice worldwide. Infections by this fungus lead to a significant reduction in rice yields and threats to food security. To gain better insight into growth and cell death in M. oryzae during infection, we characterized two predicted M. oryzae metacaspase proteins, MoMca1 and MoMca2. These proteins appear to be functionally redundant and are able to complement the yeast Yca1 homologue. Biochemical analysis revealed that M. oryzae metacaspases exhibited Ca2+ dependent caspase activity in vitro. Deletion of both MoMca1 and MoMca2 in M. oryzae resulted in reduced sporulation, delay in conidial germination and attenuation of disease severity. In addition, the double ΔMomca1mca2 mutant strain showed increased radial growth in the presence of oxidative stress. Interestingly, the ΔMomca1mca2 strain showed an increase accumulation of insoluble aggregates compared to the wild-type strain during vegetative growth. Our findings suggest that MoMca1 and MoMca2 promote the clearance of insoluble aggregates in M. oryzae, demonstrating the important role these metacaspases have in fungal protein homeostasis. Furthermore, these metacaspase proteins may play additional roles, like in regulating stress responses, that would help maintain the fitness of fungal cells required for host infection.IMPORTANCEMagnaporthe oryzae causes rice blast disease that threatens global food security by resulting in the severe loss of rice production every year. A tightly regulated life cycle allows M. oryzae to disarm the host plant immune system during its biotrophic stage before triggering plant cell death in its necrotrophic stage. The ways M. oryzae navigates its complex life cycle remains unclear. This work characterizes two metacaspase proteins with peptidase activity in M. oryzae that are shown to be involved in the regulation of fungal growth and development prior to infection by potentially helping maintain fungal fitness. This study provides new insight into the role of metacaspase proteins in filamentous fungi by illustrating the delays in M. oryzae morphogenesis in the absence of these proteins. Understanding the mechanisms by which M. oryzae morphology and development promote its devastating pathogenicity may lead to the emergence of proper methods for disease control.

scholarly journals Hurricane Juan (2003). Part I: A Diagnostic and Compositing Life Cycle Study

2006 ◽  
Vol 134 (7) ◽  
pp. 1725-1747 ◽  
Author(s):  
Ron McTaggart-Cowan ◽  
Eyad H. Atallah ◽  
John R. Gyakum ◽  
Lance F. Bosart
Keyword(s):  
Life Cycle ◽  
East Coast ◽  
Leading Edge ◽  
High Amplitude ◽  
Complex Life Cycle ◽  
Low Latitude ◽  
Initial Development ◽  
Easterly Wave ◽  
Case Diagnosis

Abstract A detailed analysis of the complex life cycle of Hurricane Juan (in 2003) is undertaken to elucidate the structures and forcings that prevailed over the period leading up to the hurricane’s landfall in Halifax, Nova Scotia, Canada. Despite the presence of easterly wave precursors, Hurricane Juan’s initial development is shown to occur in a baroclinic environment beneath a low-latitude potential vorticity streamer. This feature interacts with a lower-level shear line as the incipient vortex begins to effectively focus ascent and convection. The system undergoes a slow tropical transition over a period of several days as the deep-layer shear over the developing storm decreases. The hurricane is repeatedly perturbed by subsynoptic-scale waves traveling along the leading edge of a large upstream trough. However, Hurricane Juan maintains its tropical structure despite its relatively high formation latitude (28°N) and its northward trajectory. The unusual persistence of the storm’s tropical nature as it propagates northward is of primary interest in this study. In particular, the role of persistent ridging along the east coast of North America is investigated both in high-resolution analyses for Hurricane Juan and in a compositing framework. Dynamic tropopause, quasigeostrophic, and modified Eady model diagnostics are used to elucidate the interactions between Hurricane Juan and this amplified midlatitude flow. Given the strength and persistence of the anomalous ridge–trough couplet both in the case diagnosis and in the composite fields, the study concludes that the presence of prestorm, high-amplitude ridging along the east coast likely reinforced by diabatic ridging downshear of the storm itself produces an environment both dynamically and thermodynamically conducive to the high-latitude landfall of hurricanes still in the tropical phase.

scholarly journals Structural role of essential light chains in the apicomplexan glideosome

2019 ◽  
Author(s):  
Samuel Pazicky ◽  
Karthikeyan Dhamotharan ◽  
Karol Kaszuba ◽  
Haydyn Mertens ◽  
Tim Gilberger ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Light Chain ◽  
Structural Information ◽  
Host Cells ◽  
Light Chains ◽  
Apicomplexan Parasites ◽  
Membrane Complex ◽  
C Terminus ◽  
Inner Membrane Complex

AbstractApicomplexan parasites, such as Plasmodium falciparum and Toxoplasma gondii, traverse the host tissues and invade the host cells exhibiting a specific type of motility called gliding. The molecular mechanism of gliding lies in the actin-myosin motor localized to the intermembrane space between the plasma membrane and inner membrane complex (IMC) of the parasites. Myosin A (MyoA) is a part of the glideosome, a large multi-protein complex, which is anchored in the outer membrane of the IMC. MyoA is bound to the proximal essential light chain (ELC) and distal myosin light chain (MLC1), which further interact with the glideosome associated proteins GAP40, GAP45 and GAP50. Whereas structures of several individual glideosome components and small dimeric complexes have been solved, structural information concerning the interaction of larger glideosome subunits and their role in glideosome function still remains to be elucidated. Here, we present structures of a T. gondii trimeric glideosome sub complex composed of a myosin A light chain domain with bound MLC1 and TgELC1 or TgELC2. Regardless of the differences between the secondary structure content observed for free P. falciparum PfELC and T. gondii TgELC1 or TgELC2, the proteins interact with a conserved region of TgMyoA to form structurally conserved complexes. Upon interaction, the essential light chains undergo contraction and induce α-helical structure in the myosin A C-terminus, stiffening the myosin lever arm. The complex formation is further stabilized through binding of a single calcium ion to T. gondii ELCs. Our work provides an important step towards the structural understanding of the entire glideosome and uncovering the role of its members in parasite motility and invasion.Author summaryApicomplexans, such as Toxoplasma gondii or the malaria agent Plasmodium falciparum, are small unicellular parasites that cause serious diseases in humans and other animals. These parasites move and infect the host cells by a unique type of motility called gliding. Gliding is empowered by an actin-myosin molecular motor located at the periphery of the parasites. Myosin interacts with additional proteins such as essential light chains to form the glideosome, a large protein assembly that anchors myosin in the inner membrane complex. Unfortunately, our understanding of the glideosome is insufficient because we lack the necessary structural information. Here we describe the first structures of trimeric glideosome sub complexes of T. gondii myosin A bound to two different light chain combinations, which show that T. gondii and P. falciparum form structurally conserved complexes. With an additional calcium-free complex structure, we demonstrate that calcium binding does not change the formation of the complexes, although it provides them with substantial stability. With additional data, we propose that the role of the essential light chains is to enhance myosin performance by inducing secondary structure in the C-terminus of myosin A. Our work represents an important step in unveiling the gliding mechanism of apicomplexan parasites.

scholarly journals Role of Two Metacaspases in Development and Pathogenicity of the Rice Blast Fungus Magnaporthe oryzae

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jessie Fernandez ◽  
Victor Lopez ◽  
Lisa Kinch ◽  
Mariel A. Pfeifer ◽  
Hillery Gray ◽  
...  
Keyword(s):  
Cell Death ◽  
Food Security ◽  
Life Cycle ◽  
Magnaporthe Oryzae ◽  
Rice Blast ◽  
Rice Blast Disease ◽  
Blast Disease ◽  
Complex Life Cycle ◽  
Content Type

ABSTRACT Rice blast disease caused by Magnaporthe oryzae is a devastating disease of cultivated rice worldwide. Infections by this fungus lead to a significant reduction in rice yields and threats to food security. To gain better insight into growth and cell death in M. oryzae during infection, we characterized two predicted M. oryzae metacaspase proteins, MoMca1 and MoMca2. These proteins appear to be functionally redundant and can complement the yeast Yca1 homologue. Biochemical analysis revealed that M. oryzae metacaspases exhibited Ca2+-dependent caspase activity in vitro. Deletion of both MoMca1 and MoMca2 in M. oryzae resulted in reduced sporulation, delay in conidial germination, and attenuation of disease severity. In addition, the double ΔMomca1mca2 mutant strain showed increased radial growth in the presence of oxidative stress. Interestingly, the ΔMomca1mca2 strain showed an increased accumulation of insoluble aggregates compared to the wild-type strain during vegetative growth. Our findings suggest that MoMca1 and MoMca2 promote the clearance of insoluble aggregates in M. oryzae, demonstrating the important role these metacaspases have in fungal protein homeostasis. Furthermore, these metacaspase proteins may play additional roles, like in regulating stress responses, that would help maintain the fitness of fungal cells required for host infection. IMPORTANCE Magnaporthe oryzae causes rice blast disease that threatens global food security by resulting in the severe loss of rice production every year. A tightly regulated life cycle allows M. oryzae to disarm the host plant immune system during its biotrophic stage before triggering plant cell death in its necrotrophic stage. The ways M. oryzae navigates its complex life cycle remain unclear. This work characterizes two metacaspase proteins with peptidase activity in M. oryzae that are shown to be involved in the regulation of fungal growth and development prior to infection by potentially helping maintain fungal fitness. This study provides new insights into the role of metacaspase proteins in filamentous fungi by illustrating the delays in M. oryzae morphogenesis in the absence of these proteins. Understanding the mechanisms by which M. oryzae morphology and development promote its devastating pathogenicity may lead to the emergence of proper methods for disease control.

scholarly journals Functional Diversity of the Schistosoma mansoni Tyrosine Kinases

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Lívia G. A. Avelar ◽  
Laila A. Nahum ◽  
Luiza F. Andrade ◽  
Guilherme Oliveira
Keyword(s):  
Life Cycle ◽  
Schistosoma Mansoni ◽  
Tyrosine Kinases ◽  
Large Body ◽  
Protein Domain ◽  
Complex Life Cycle ◽  
Main Process ◽  
Parasite Life Cycle ◽  
Causative Agents

Schistosoma mansoni, one of the causative agents of schistosomiasis, has a complex life cycle infecting over 200 million people worldwide. Such a successful and prolific parasite life cycle has been shown to be dependent on the adaptive interaction between the parasite and hosts. Tyrosine kinases (TKs) play a key role in signaling pathways as demonstrated by a large body of experimental work in eukaryotes. Furthermore, comparative genomics have allowed the identification of TK homologs and provided insights into the functional role of TKs in several biological systems. Finally, TK structural biology has provided a rational basis for obtaining selective inhibitors directed to the treatment of human diseases. This paper covers the important aspects of the phospho-tyrosine signaling network in S. mansoni, Caenorhabditis elegans, and humans, the main process of functional diversification of TKs, that is, protein-domain shuffling, and also discusses TKs as targets for the development of new anti-schistosome drugs.

scholarly journals The cellular and molecular basis for malaria parasite invasion of the human red blood cell

2012 ◽  
Vol 198 (6) ◽  
pp. 961-971 ◽  
Author(s):  
Alan F. Cowman ◽  
Drew Berry ◽  
Jake Baum
Keyword(s):  
Life Cycle ◽  
Blood Stream ◽  
Complex Life Cycle ◽  
Host Immune System ◽  
Asexual Parasite ◽  
Protozoan Parasites ◽  
Parasite Invasion ◽  
Genus Plasmodium ◽  
Underlying Mechanisms ◽  
Significant Effort

Malaria is a major disease of humans caused by protozoan parasites from the genus Plasmodium. It has a complex life cycle; however, asexual parasite infection within the blood stream is responsible for all disease pathology. This stage is initiated when merozoites, the free invasive blood-stage form, invade circulating erythrocytes. Although invasion is rapid, it is the only time of the life cycle when the parasite is directly exposed to the host immune system. Significant effort has, therefore, focused on identifying the proteins involved and understanding the underlying mechanisms behind merozoite invasion into the protected niche inside the human erythrocyte.

scholarly journals Expression and Physiological Role of Three Myxococcus xanthus Copper-Dependent P1B-Type ATPases during Bacterial Growth and Development

2010 ◽  
Vol 76 (18) ◽  
pp. 6077-6084 ◽  
Author(s):  
Aurelio Moraleda-Muñoz ◽  
Juana Pérez ◽  
Antonio Luis Extremera ◽  
José Muñoz-Dorado
Keyword(s):  
Life Cycle ◽  
Expression Profiles ◽  
Myxococcus Xanthus ◽  
Physiological Role ◽  
Copper Homeostasis ◽  
Cellular Damage ◽  
Complex Life Cycle ◽  
Sequence Motifs ◽  
Dual Effect

ABSTRACT Myxococcus xanthus is a soil-dwelling bacterium that exhibits a complex life cycle comprising social behavior, morphogenesis, and differentiation. In order to successfully complete this life cycle, cells have to cope with changes in their environment, among which the presence of copper is remarkable. Copper is an essential transition metal for life, but an excess of copper provokes cellular damage by oxidative stress. This dual effect forces the cells to maintain a tight homeostasis. M. xanthus encodes a large number of genes with similarities to others reported previously to be involved in copper homeostasis, most of which are redundant. We have identified three genes that encode copper-translocating P1B-ATPases (designated copA, copB, and copC) that exhibit the sequence motifs and modular organizations of those that extrude Cu+. The expression of the ATPase copC has not been detected, but copA and copB are differentially regulated by the addition of external copper. However, while copB expression peaks at 2 h, copA is expressed at higher levels, and the maximum is reached much later. The fact that these expression profiles are nearly identical to those exhibited by the multicopper oxidases cuoA and cuoB suggests that the pairs CuoB-CopB and CuoA-CopA sequentially function to detoxify the cell. The deletion of any ATPase alters the expression profiles of other genes involved in copper homeostasis, such as the remaining ATPases or the Cus systems, yielding cells that are more resistant to the metal.

scholarly journals The Role of Palmitoylation for Protein Recruitment to the Inner Membrane Complex of the Malaria Parasite

2014 ◽  
Vol 290 (3) ◽  
pp. 1712-1728 ◽  
Author(s):  
Johanna Wetzel ◽  
Susann Herrmann ◽  
Lakshmipuram Seshadri Swapna ◽  
Dhaneswar Prusty ◽  
Arun T. John Peter ◽  
...  
Keyword(s):  
Malaria Parasite ◽  
Inner Membrane ◽  
Membrane Complex ◽  
Inner Membrane Complex ◽  
Protein Recruitment

scholarly journals The esophageal gland mediates host immune evasion by the human parasiteSchistosoma mansoni

2020 ◽  
Vol 117 (32) ◽  
pp. 19299-19309
Author(s):  
Jayhun Lee ◽  
Tracy Chong ◽  
Phillip A. Newmark
Keyword(s):  
Stem Cells ◽  
Life Cycle ◽  
Immune Evasion ◽  
Blood Feeding ◽  
Life Cycle Stage ◽  
Complex Life Cycle ◽  
Mammalian Host ◽  
Immunodeficient Mice ◽  
Immune Evasion Mechanism ◽  
Esophageal Gland

Schistosomes are parasitic flatworms that cause schistosomiasis, a neglected tropical disease affecting over 200 million people. Schistosomes develop multiple body plans while navigating their complex life cycle, which involves two different hosts: a mammalian definitive host and a molluscan intermediate host. Their survival and propagation depend upon proliferation and differentiation of stem cells necessary for parasite homeostasis and reproduction. Infective larvae released from snails carry a handful of stem cells that serve as the likely source of new tissues as the parasite adapts to life inside the mammalian host; however, the role of these stem cells during this critical life cycle stage remains unclear. Here, we characterize stem cell fates during early intramammalian development. Surprisingly, we find that the esophageal gland, an accessory organ of the digestive tract, develops before the rest of the digestive system is formed and blood feeding is initiated, suggesting a role in processes beyond nutrient uptake. To explore such a role, we examine schistosomes that lack the esophageal gland due to knockdown of a forkhead-box transcription factor,Sm-foxA, which blocks development and maintenance of the esophageal gland, without affecting the development of other somatic tissues. Intriguingly, schistosomes lacking the esophageal gland die after transplantation into naive mice, but survive in immunodeficient mice lacking B cells. We show that parasites lacking the esophageal gland are unable to lyse ingested immune cells within the esophagus before passing them into the gut. These results unveil an immune-evasion mechanism mediated by the esophageal gland, which is essential for schistosome survival and pathogenesis.

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