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Parasitology,
2012]
Serine protease inhibitors (serpins) are a superfamily of structurally conserved proteins that inhibit serine proteases and play key physiological roles in numerous biological systems such as blood coagulation, complement activation and inflammation. A number of serpins have now been identified in parasitic helminths with putative involvement in immune regulation and in parasite survival through interference with the host immune response. This review describes the serpins and smapins (small serine protease inhibitors) that have been identified in Ascaris spp., Brugia malayi, Ancylostoma caninum Onchocerca volvulus, Haemonchus contortus, Trichinella spiralis, Trichostrongylus vitrinus, Anisakis simplex, Trichuris suis, Schistosoma spp., Clonorchis sinensis, Paragonimus westermani and Echinococcus spp. and discusses their possible biological functions, including roles in host-parasite interplay and their evolutionary relationships.
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Cell,
2004]
In this issue of Cell, Inoue et al. (2004) reports that LIN-18, an atypical receptor tyrosine kinase related to mammalian Ryk and Drosophila Derailed, mediates Wnt signaling in parallel to LIN-17/Frizzled (Fz) during worm vulval development. LIN-18/Ryk and LIN-17/Fz appear to exhibit distinct Wnt specificity, and surprisingly, the LIN-18 intracellular domain may be dispensable.
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Methods,
2015]
PTEN (phosphatase and tensin homolog deleted on chromosome 10) has important roles in tumor suppression, metabolism, and development, yet its regulators, effectors, and functions are not fully understood. DAF-18 is the PTEN ortholog in Caenorhabditis elegans. DAF-18's role is highly conserved to human PTEN, and can be functionally replaced by human PTEN. Thus C. elegans provides a valuable model to study PTEN. This review assesses current and emerging methods to study DAF-18's regulators and functions in C. elegans. We propose genetic modify screens to identify genes that interact with
daf-18/PTEN. These genes are potential targets for anticancer drug therapies. We also provide a review on the roles DAF-18/PTEN has during C. elegans development and how studying these physiological roles can provide mechanistic insight on DAF-18/PTEN function.
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Ciba Found Symp,
1987]
Human lymphatic filariasis is caused mainly by Wuchereria bancrofti, Brugia malayi and Brugia timori. Of the estimated 90.2 million people infected, more than 90% have bancroftian and less than 10% brugian filariasis. The distribution and transmission of the disease are closely associated with socioeconomic and behavioural factors in endemic populations. Urban W. bancrofti infection, as seen in South-East Asia, is related to poor urban sanitation, which leads to intense breeding of Culex quiquefasciatus, the principal vector. Rural strains of W. bancrofti are transmitted primarily by Anopheles spp. and Aedes spp. mosquitoes. Brugian filariasis is mainly a rural disease transmitted by Mansonia, Anopheles and Aedes spp. mosquitoes. The periodic form of B. malayi is principally a human parasite, whereas the subperiodic form is zoonotically transmitted in some countries. The control of filariasis has relied on chemotherapy, vector control and reduction of human-vector contact. Although eradication of W. bancrofti and periodic B. malayi can be achieved, it is possible only to reduce transmission of zoonotic subperiodic B. malayi in some areas. A rational approach to control should consider ecological, socioeconomic and behavioural factors and, where feasible, integrate control programmes into the delivery system for primary health care.
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Trends Genet,
2008]
Induced mutants in the nematode Caenorhabditis elegans are used to study genetic pathways of processes ranging from aging to behavior. The effects of such mutations are usually analyzed in a single wildtype background: N2. However, studies in other species demonstrate that the phenotype(s) of induced mutations can vary widely depending on the genetic background. Moreover, induced mutations in one genetic background do not reveal the allelic effects that segregate in natural populations and contribute to phenotypic variation. Because other wildtype Caenorhabditis spp., including C. elegans, are now available, we review how current mapping resources and methodologies within and between species support the use of Caenorhabditis spp. for studying genetic variation, with a focus on pathways associated with human disease.
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J Fungi (Basel),
2020]
<i>Malassezia</i> is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated with the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interactions of <i>Malassezia</i> spp., and unraveling this implies the implementation of infection models. In this mini review, we present different models that have been implemented in fungal infections studies with greater attention to <i>Malassezia</i> spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have been shown to have reliable results, which correlate with those obtained from mammalian models. Examples of alternative models are <i>Caenorhabditis elegans</i>, <i>Drosophila melanogaster</i>, <i>Tenebrio molitor</i>, and <i>Galleria mellonella</i>. These are invertebrates that have been implemented in the study of <i>Malassezia</i> spp. infections in order to identify differences in virulence between <i>Malassezia</i> species.
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Korean J Parasitol,
2015]
DEAD/DExH-box RNA helicases catalyze the folding and remodeling of RNA molecules in prokaryotic and eukaryotic cells, as well as in many viruses. They are characterized by the presence of the helicase domain with conserved motifs that are essential for ATP binding and hydrolysis, RNA interaction, and unwinding activities. Large families of DEAD/DExH-box proteins have been described in different organisms, and their role in all molecular processes involving RNA, from transcriptional regulation to mRNA decay, have been described. This review aims to summarize the current knowledge about DEAD/DExH-box proteins in selected protozoan and nematode parasites of medical importance worldwide, such as Plasmodium falciparum, Leishmania spp., Trypanosoma spp., Giardia lamblia, Entamoeba histolytica, and Brugia malayi. We discuss the functional characterization of several proteins in an attempt to understand better the molecular mechanisms involving RNA in these pathogens. The current data also highlight that DEAD/DExH-box RNA helicases might represent feasible drug targets due to their vital role in parasite growth and development.
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Philos Trans R Soc Lond B Biol Sci,
2024]
Among nematodes, the free-living model organism <i>Caenorhabditis elegans</i> boasts the most advanced portfolio of high-quality omics data. The resources available for parasitic nematodes, including <i>Strongyloides</i> spp., however, are lagging behind. While <i>C. elegans</i> remains the most tractable nematode and has significantly advanced our understanding of many facets of nematode biology, <i>C. elegans</i> is not suitable as a surrogate system for the study of parasitism and it is important that we improve the omics resources available for parasitic nematode species. Here, we review the omics data available for <i>Strongyloides</i> spp<i>.</i> and compare the available resources to those for <i>C. elegans</i> and other parasitic nematodes. The advancements in <i>C. elegans</i> omics offer a blueprint for improving omics-led research in <i>Strongyloides</i>. We suggest areas of priority for future research that will pave the way for expansions in omics resources and technologies. This article is part of the Theo Murphy meeting issue '<i>Strongyloides</i>: omics to worm-free populations'.
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Southeast Asian J Trop Med Public Health,
1993]
The lymphatic filarial parasites which affect about 90 million people worldwide have similar host-parasite relationships in man. They are all able to survive, reproduce and cause chronic infections if they can successfully evade the protective responses of the host. Studies to investigate the wide spectrum of clinical manifestations of the infection even among those living in similar endemic areas and with presumed equal exposure to infective larvae, have been hampered by the lack of animal models showing similar host-parasite responses. The recent use of the nude mouse infected with Brugia spp, and the leaf-monkey (Presbytis spp) infected with B. malayi or Wuchereria spp for the study of immune responses and the associated pathology of these infections, has elucidated some of the host protective immune responses as well as the associated immunopathological reactions. The successfully entrenched parasite elicits minimal reactions and pathology, but with the onset of effective host responses, whether assisted by chemotherapy, development of protective immunity or both, severe inflammatory responses may occur. The role of such immune mediated response in determining subsequent pathology will probably be dependent on the frequency and duration of these episodes, but these have yet to be defined. Prenatal and perinatal sensitization by filarial antigens are postulated to result in tolerance and/or modification of immune responses to subsequent infections. A role for genetic predisposition to certain clinical outcomes, for example, the development of elephantiasis, has been postulated but needs further study. Advances have also been achieved in defining those parasite antigens/products involved in eliciting or suppressing protective and other immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)
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J Fungi (Basel),
2018]
Dimorphic fungi can be found in the yeast form during infection and as hyphae in the environment and are responsible for a large number of infections worldwide. Invertebrate animals have been shown to be convenient models in the study of fungal infections. These models have the advantages of being low cost, have no ethical issues, and an ease of experimentation, time-efficiency, and the possibility of using a large number of animals per experiment compared to mammalian models. Invertebrate animal models such as <i>Galleria mellonella</i>, <i>Caenorhabditis elegans</i>, and <i>Acanthamoeba</i><i>castellanii</i> have been used to study dimorphic fungal infections in the context of virulence, innate immune response, and the efficacy and toxicity of antifungal agents. In this review, we first summarize the features of these models. In this aspect, the growth temperature, genome sequence, availability of different strains, and body characteristics should be considered in the model choice. Finally, we discuss the contribution and advances of these models, with respect to dimorphic fungi <i>Paracoccidioides</i> spp., <i>Histoplasma capsulatum</i>, <i>Blastomyces dermatitidis</i>, <i>Sporothrix</i> spp., and <i>Talaromyces marneffei (Penicillium marneffei)</i>.