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

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.

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1628
Author(s):  
Rodolpho Ornitz Oliveira Souza ◽  
Marcell Crispim ◽  
Ariel Mariano Silber ◽  
Flávia Silva Damasceno

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.


2004 ◽  
Vol 82 (2) ◽  
pp. 357-374 ◽  
Author(s):  
Philip T LoVerde ◽  
Edward G Niles ◽  
Ahmed Osman ◽  
Wenjie Wu

Schistosome parasites are muticellular eucaryotic organisms with a complex life cycle that involves mammalian and snail hosts. Unlike other trematode parasites, schistosomes (along with the Didymozoidae) have evolved separate sexes or dioecy. Sex is determined by a chromosomal mechanism. The dioecious state created an opportunity for the sexes to play a role in schistosome evolution that has resulted in an interesting interplay between the sexes. The classical observation, made more than 50 years ago, is that female schistosomes do not develop unless a male worm is present. Studies up through the 1990s focused on dissecting the role of the sexes in mate attraction, mate choice, mating behavior, female growth, female reproductive development, egg production, and other sex-evolved functions. In the mid-1980s, studies began to address the molecular events of male–female interactions. The classic morphological observation that female schistosomes do not complete reproductive development unless a male worm is present has been redefined in molecular terms. The male by an unknown mechanism transduces a signal that regulates female gene expression in a stage-, tissue-, and temporal-specific manner. A number of female-specific genes have been identified, along with signaling pathways and nuclear receptors, that play a role in female reproductive development. In addition, a number of host factors such as cytokines have also been demonstrated to affect adult male and female development and egg production. This review focuses on the biological interactions of the male and female schistosome and the role of parasite and host factors in these interactions as they contribute to the life cycle of Schistosoma mansoni.


Author(s):  
Betty Ruth Jones ◽  
Steve Chi-Tang Pan

INTRODUCTION: Schistosomiasis has been described as “one of the most devastating diseases of mankind, second only to malaria in its deleterious effects on the social and economic development of populations in many warm areas of the world.” The disease is worldwide and is probably spreading faster and becoming more intense than the overall research efforts designed to provide the basis for countering it. Moreover, there are indications that the development of water resources and the demands for increasing cultivation and food in developing countries may prevent adequate control of the disease and thus the number of infections are increasing.Our knowledge of the basic biology of the parasites causing the disease is far from adequate. Such knowledge is essential if we are to develop a rational approach to the effective control of human schistosomiasis. The miracidium is the first infective stage in the complex life cycle of schistosomes. The future of the entire life cycle depends on the capacity and ability of this organism to locate and enter a suitable snail host for further development, Little is known about the nervous system of the miracidium of Schistosoma mansoni and of other trematodes. Studies indicate that miracidia contain a well developed and complex nervous system that may aid the larvae in locating and entering a susceptible snail host (Wilson, 1970; Brooker, 1972; Chernin, 1974; Pan, 1980; Mehlhorn, 1988; and Jones, 1987-1988).


2020 ◽  
Author(s):  
Jessie Fernandez ◽  
Victor Lopez ◽  
Lisa Kinch ◽  
Mariel A. Pfeifer ◽  
Hillery Gray ◽  
...  

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.


2011 ◽  
Vol 51 ◽  
pp. 127-136 ◽  
Author(s):  
Isabelle Coppens

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.


2006 ◽  
Vol 134 (7) ◽  
pp. 1725-1747 ◽  
Author(s):  
Ron McTaggart-Cowan ◽  
Eyad H. Atallah ◽  
John R. Gyakum ◽  
Lance F. Bosart

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.


mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jessie Fernandez ◽  
Victor Lopez ◽  
Lisa Kinch ◽  
Mariel A. Pfeifer ◽  
Hillery Gray ◽  
...  

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.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Elton J. R. Vasconcelos ◽  
Lucas F. daSilva ◽  
David S. Pires ◽  
Guilherme M. Lavezzo ◽  
Adriana S. A. Pereira ◽  
...  

Parasitology ◽  
2009 ◽  
Vol 136 (12) ◽  
pp. 1395-1402 ◽  
Author(s):  
KEITH VICKERMAN

SUMMARYThe man in-the-street who frequently asks the question “Why am I here?” finds even more difficulty with the question “Why are parasites here?” The public's distaste for parasites (and by implication, for parasitologists!) is therefore understandable, as maybe was the feeling of early 20th century biologists that parasites were a puzzle because they did not conform to the then widely held association between evolution and progress, let alone the reason why a benevolent Creator should have created them. In mid-century, the writer, contemplating a career in parasitology was taken aback when he found that extolled contemporary biologists disdained parasites or thought little of parasitology as an intellectual subject. These attitudes reflected a lack of appreciation of the important role of parasites in generating evolutionary novelty and speciation, also unawareness of the value of parasite life-cycle studies for formulating questions of wider significance in biology, deficiencies which were gratifyingly beginning to be remedied in the latter half of the century.


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