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Molecular and Biochemical Parasitology May 2022Strongyloides' developmental switch between direct, parasitic and indirect, free-living development has intrigued, confused, and fascinated biologists since it was first...
Strongyloides' developmental switch between direct, parasitic and indirect, free-living development has intrigued, confused, and fascinated biologists since it was first discovered more than 100 years ago. Proximately, the switch is controlled by environmental conditions that developing larvae are exposed to, but genotypes differ in their sensitivity to these cues. Ultimately, selection will act on this switch to generate a direct vs. indirect phenotype that maximises a genotype's fitness, but we have a poor understanding of the relative fitness advantages of these different routes of development. Mechanistically, the switch senses and transduces environmental cues, integrates signals that are then used to make a developmental decision which is then enacted. Seeking to understand the molecular form of this process has focussed on the C. elegans dauer hypothesis, but this has been found to be wanting. So, we argue that the time has come to move beyond the dauer hypothesis and better refine our question to ask: What is it that controls the variation in developmental switching among Strongyloides genotypes? We discuss approaches to achieve this research aim that now lies within our grasp.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Larva; Strongyloides
PubMed: 35413360
DOI: 10.1016/j.molbiopara.2022.111477 -
Parasites & Vectors Jun 2016Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human...
BACKGROUND
Strongyloidiasis is a parasitic disease widely present in tropical and subtropical areas. Strongyloides stercoralis represents the main species that infects human beings. Ivermectin is the current drug of choice; however, issues related with treatment failure in patients with diabetes or infected with T-lymphotropic virus-1 make the identification of new molecules for alternative treatment a priority. In the present study, the activity of sphingosine-related aminoalcohol and diamine were evaluated against Strongyloides venezuelensis third-stage larva (L3) cultures and experimental infections in mice.
METHODS
The efficacy of each compound against L3 was assessed using both XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and microscopic observation with concentrations ranging from 1 to 350 μM. Cytotoxicity was evaluated using J774.2 macrophage cell line and XTT assay. Lethal concentration 50 (LC50), selectivity index (SI) and structure-activity relationships were established. The activity compounds 4 (2-(ethylamino) hexadecan-1-ol), 6 (2-(butylamino) hexadecan-1-ol), 17 (tert-butyl N-(1-aminododecan-2-yl) carbamate) and 18 (tert-butyl N-(1-aminohexadecan-2-yl) carbamate) were further assessed against experimental S. venezuelensis infections in CD1 mice measuring reductions in the numbers of parthenogenetic females and egg passed in faeces. Mice were infected with 3,000 L3 and treated with 20 mg/kg/day for five days.
RESULTS
In the screening study of 15 aminoalcohols [lauryl (n = 9); palmityl (n = 13); stearyl (n = 15) and alcohol derivatives], the presence of a palmitol chain was associated with the highest efficacy against L3 (LC50 31.9-39.1 μM). Alkylation of the 2-amino group with medium size fragments as ethyl or n-butyl showed the best larvicidal activity. The dialkylation did not improve efficacy. Aminoalcohols 4 and 6 showed the highest SI (1.5 and 1.6, respectively). With respect to diamine derivative compounds, a chain size of sixteen carbon atoms (palmitoyl chain, n = 13), and the alkylation of the 2-amino group with medium-sized fragments, were associated with the highest lethal activities. The presence of carbamoyl group in diamines 17 and 18 yielded high SI (1.7 and 1.4, respectively). Infected mice treated with aminoalcohol 6 showed reduction in parthenogenetic females (59 %) and eggs in faeces (51 %).
CONCLUSIONS
These results support the potentiality of aminoalcohol and diamine sphingosine-related compounds as suitable prototypes for developing new promising drugs against strongyloidiasis.
Topics: Amino Alcohols; Animals; Anthelmintics; Diamines; Male; Mice; Molecular Structure; Rats; Strongyloides; Strongyloidiasis; Structure-Activity Relationship
PubMed: 27353595
DOI: 10.1186/s13071-016-1648-5 -
Parasites & Vectors Nov 2023Ribosome biogenesis is the process of assembling ribosome complexes that regulate cell proliferation and differentiation with potential regulatory effects on...
BACKGROUND
Ribosome biogenesis is the process of assembling ribosome complexes that regulate cell proliferation and differentiation with potential regulatory effects on development. Many factors regulate ribosome biological processes. Nin one binding protein (Nob1) has received widespread attention as key genes regulating ribosome biogenesis-the 3' end of the 20S rRNA is cleaved by Nob1 at cleavage site D to form 18S rRNA, generating translationally capable 40S subunit. As a ribosome biogenesis factor, Nob1 may regulate the development of organisms, but almost nothing is known about the function of Nob1 for any parasitic nematode. We explored the functional role of NOBP-1 (the homologous gene of Nob1) encoding gene from a parasitic nematode-Strongyloides stercoralis.
METHODS
The full-length cDNA, gDNA and promoter region of Ss-nobp-1 was identified using protein BLAST in WormBase ParaSite according to the Caenorhabditis elegans NOBP-1 sequence to analyze the gene structure. RNA sequencing (RNA-seq) data in wormbase were retrieved and analyzed to assess the transcript abundance of Ss-nobp-1 in seven developmental stages of S. stercoralis. The standard method for gonadal microinjection of constructs was carried out to determine the anatomic expression patterns of Ss-nobp-1. The interaction between Ss-NOBP-1 and partner of NOBP-1 (Ss-PNO-1) was assessed by yeast two-hybridization and bimolecular fluorescence complementarity (BiFC) experiments.
RESULTS
The NOBP-1 encoding gene Ss-nopb-1 from the zoonotic parasite S. stercoralis has been isolated and characterized. The genomic DNA representing Ss-nobp-1 includes a 1599-bp coding region and encodes a protein comprising 403 amino acids (aa), which contains conserved PIN domain and zinc ribbon domain. RNA-seq analysis revealed that Ss-nobp-1 transcripts are present throughout the seven developmental stages in S. stercoralis and have higher transcription levels in iL3, L3 and P Female. Ss-nobp-1 is expressed mainly in the intestine of transgenic S. stercoralis larvae, and there is a direct interaction between Ss-NOBP-1 and Ss-PNO-1.
CONCLUSIONS
Collectively, Ss-NOBP-1 has a potential role in embryo formation and the infective process, and findings from this study provide a sound foundation for investigating its function during the development of parasitic nematode.
Topics: Animals; Female; Strongyloides stercoralis; Animals, Genetically Modified; Caenorhabditis elegans; Larva
PubMed: 37924155
DOI: 10.1186/s13071-023-05940-9 -
PLoS Pathogens Oct 2017Parasitic nematodes infect over 1 billion people worldwide and cause some of the most common neglected tropical diseases. Despite their prevalence, our understanding of...
Parasitic nematodes infect over 1 billion people worldwide and cause some of the most common neglected tropical diseases. Despite their prevalence, our understanding of the biology of parasitic nematodes has been limited by the lack of tools for genetic intervention. In particular, it has not yet been possible to generate targeted gene disruptions and mutant phenotypes in any parasitic nematode. Here, we report the development of a method for introducing CRISPR-Cas9-mediated gene disruptions in the human-parasitic threadworm Strongyloides stercoralis. We disrupted the S. stercoralis twitchin gene unc-22, resulting in nematodes with severe motility defects. Ss-unc-22 mutations were resolved by homology-directed repair when a repair template was provided. Omission of a repair template resulted in deletions at the target locus. Ss-unc-22 mutations were heritable; we passed Ss-unc-22 mutants through a host and successfully recovered mutant progeny. Using a similar approach, we also disrupted the unc-22 gene of the rat-parasitic nematode Strongyloides ratti. Our results demonstrate the applicability of CRISPR-Cas9 to parasitic nematodes, and thereby enable future studies of gene function in these medically relevant but previously genetically intractable parasites.
Topics: Animals; Animals, Genetically Modified; Calmodulin-Binding Proteins; Genetic Engineering; Humans; Muscle Proteins; Mutagenesis; Rats; Strongyloides ratti; Strongyloides stercoralis
PubMed: 29016680
DOI: 10.1371/journal.ppat.1006675 -
WMJ : Official Publication of the State... Jul 2023Coccidioidomycosis is most often an asymptomatic or mild self-limited respiratory infection, but in rare cases it can become disseminated and cause severe disease.
INTRODUCTION
Coccidioidomycosis is most often an asymptomatic or mild self-limited respiratory infection, but in rare cases it can become disseminated and cause severe disease.
CASE PRESENTATION
A 29-year-old man who was originally from Thailand and had been living in Arizona for 2 years presented with intermittent fevers, fatigue, and other nonspecific symptoms, including abdominal pain, nonbloody diarrhea, and pruritic rash. Initial laboratory values showed significant peripheral eosinophilia. Extensive evaluation revealed possible species infection. Shortly after, species fungemia was found. Fevers and symptoms resolved after adequate treatment.
DISCUSSION
Disseminated coccidioidomycosis with fungemia is very rare in immunocompetent individuals. Co-infection with species is only reported in two other case reports.
CONCLUSIONS
We report this case to raise awareness of a rare infection. In adequate epidemiological circumstances, co-infections and species should be considered in presence of fever and eosinophilia.
Topics: Male; Animals; Humans; Adult; Coccidioidomycosis; Fungemia; Coinfection; Strongyloides; Fever
PubMed: 37494652
DOI: No ID Found -
Parasites & Vectors Oct 2023Strongyloides stercoralis infection is a common neglected tropical disease distributed worldwide, mainly in tropical and subtropical climates. The impact of S....
BACKGROUND
Strongyloides stercoralis infection is a common neglected tropical disease distributed worldwide, mainly in tropical and subtropical climates. The impact of S. stercoralis infections on human health ranges from mild asymptomatic infections to chronic strongyloidiasis unnoticeable until the host is immunosuppressed. In severe strongyloidiasis, a syndrome of hyperinfection and larval dissemination to various organs can occur with high mortality rates. The diagnosis of strongyloidiasis is challenging because of the absence of a single standard reference test with high sensitivity and specificity, which also makes it difficult to estimate the accuracy of other diagnostic tests. This study aimed to evaluate, for the first time, the use of an easy-to-perform loop-mediated isothermal amplification (LAMP) colorimetric assay (named Strong-LAMP) for the molecular screening of strongyloidiasis in stool samples from patients in a low-resource endemic area in Cubal, Angola. To compare different LAMP application scenarios, the performance of the Strong-LAMP under field conditions in Angola was reassessed in a well-equipped reference laboratory in Spain and compared with a quantitative polymerase chain reaction (qPCR) method.
METHODS
A total of 192 stool samples were collected from adult population in Cubal, Angola, and examined by parasitological methods (direct saline microscopy and Baermann's technique). DNA was extracted from each stool sample using a commercial kit and tested by the colorimetric Strong-LAMP assay for the detection of Strongyloides spp. under field conditions. Furthermore, all samples were shipped to a well-equipped laboratory in Spain, reanalysed by the same procedure and compared with a qPCR method. The overall results after testing were compared.
RESULTS
Strongyloides stercoralis larvae were identified by direct saline microscopy and Baermann in a total of 10/192 (5.2%) and 18/192 (9.4%) stool samples, respectively. Other helminth and protozoan species were also identified. The Strong-LAMP-positive results were visually detected in 69/192 (35.9%) stool samples. The comparison of Strong-LAMP results in field conditions and at a reference laboratory matched in a total of 146/192 (76.0%) samples. A total of 24/192 (12.5%) stool samples tested positive by qPCR.
CONCLUSIONS
This is the first study in which colorimetric Strong-LAMP has been clinically evaluated in a resource-poor strongyloidiasis endemic area. Strong-LAMP has been shown to be more effective in screening for strongyloidiasis than parasitological methods under field conditions and qPCR in the laboratory. Our Strong-LAMP has proven to be a field-friendly and highly accurate molecular test for the diagnosis of strongyloidiasis.
Topics: Adult; Animals; Humans; Strongyloidiasis; Angola; Strongyloides stercoralis; Laboratories; Feces
PubMed: 37907997
DOI: 10.1186/s13071-023-06009-3 -
BMC Infectious Diseases Aug 2021Strongyloidiasis is a disease of great public health significance, caused by the parasitic nematodes Strongyloides stercoralis, Strongyloides fuelleborni, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Strongyloidiasis is a disease of great public health significance, caused by the parasitic nematodes Strongyloides stercoralis, Strongyloides fuelleborni, and Strongyloides fuelleborni subsp. kellyi. This systematic review and meta-analysis aimed to assess the prevalence of Strongyloides stercoralis infection in Peru.
METHODS
The review was based on a literature search in PubMed, SciELO and Google Scholar using the key words or root words "strongyl*" AND "Peru" on 15 July 2020. Eligible studies were published from 1 January 1981 to 15 July 2020 and written in English, Spanish, Italian, or French.
RESULTS
We included 21 papers in the analysis. Studies were heterogeneous in terms of study population and diagnostic methods (e.g. Baermann technique, agar, Dancescu or charcoal cultures, serology, string capsule). Prevalence of S. stercoralis ranged from 0.3 to 45%. The pooled proportion of Strongyloides in the general population was 7.34% (95% CI 4.97 to 10.13%). Half the studies were designed to detect parasites in general. In studies designed to detect S. stercoralis, the most widely used diagnostic method was the Baermann technique.
CONCLUSION
Prevalence of S. stercoralis in Peru was high but varied by geographic area, techniques for stool examination, and participant characteristics.
Topics: Animals; Feces; Humans; Peru; Prevalence; Strongyloides stercoralis; Strongyloidiasis
PubMed: 34348671
DOI: 10.1186/s12879-021-06441-9 -
Clinical and Diagnostic Laboratory... May 2005We report strongyloides hyperinfection in two patients with generalized hypogammaglobulinemia from multiple myeloma and nephrotic syndrome, despite a significant... (Review)
Review
We report strongyloides hyperinfection in two patients with generalized hypogammaglobulinemia from multiple myeloma and nephrotic syndrome, despite a significant strongyloides-specific immunoglobulin G (IgG) response. In contrast to reports on animals, where human IgG was shown to be a protective antibody, our observation suggests that in humans, immunity to the infective-stage larvae is not protective against the autoinfective larvae, which are the causative agents of strongyloides hyperinfection.
Topics: Agammaglobulinemia; Animals; Antibodies, Helminth; Antibody Formation; Humans; Immunoglobulin G; Larva; Male; Middle Aged; Multiple Myeloma; Nephrotic Syndrome; Strongyloides; Strongyloidiasis
PubMed: 15879034
DOI: 10.1128/CDLI.12.5.680-682.2005 -
Parasites & Vectors Jun 2022The WHO has established a control strategy for Strongyloides stercoralis in school-aged children as well as targets and to maintain control programs for Ascaris...
BACKGROUND
The WHO has established a control strategy for Strongyloides stercoralis in school-aged children as well as targets and to maintain control programs for Ascaris lumbricoides, Trichuris trichiura and hookworms. For an efficient development of control programs, it is necessary to know the target countries around the world, as well as the areas within each country where efforts should be focused. Therefore, maps that provide information on the areas at risk for soil-transmitted helminth (STH) infections on a national and sub-national scale would allow for a better allocation of resources.
METHODS
We used the ecological niche models MaxEnt and Kuenm R library to estimate the global distribution of S. stercoralis and hookworms. We used occurrence points of both species extracted from surveys of two literature reviews and from the Global Atlas of Helminth Infection database, together with 14 raster maps of environmental variables.
RESULTS
We obtained two raster maps with the presence probability of S. stercoralis and hookworm infections at a global level and then estimated the global population at risk to be 2.6 and 3.4 billion, respectively. The population at risk was also estimated at the country level using estimations for areas as small as 25 km. A relationship was found between the probability of the presence of S. stercoralis and its prevalence, and a raster map was generated. Annual precipitation, annual temperature, soil carbon content and land cover were the main associated environmental variables. The ecological niches of Strongyloides stercoralis and hookworms had an overlap of 68%.
CONCLUSIONS
Here we provide information that can be used for developing more efficient and integrated control strategies for S. stercoralis and hookworm infections. This information can be annexed to the study of other risk factors or even other diseases to assess the health status of a community. GRAPHICAL ABSTARCT.
Topics: Ancylostomatoidea; Animals; Ascaris lumbricoides; Child; Ecosystem; Feces; Helminthiasis; Hookworm Infections; Humans; Prevalence; Soil; Strongyloides stercoralis; Strongyloidiasis
PubMed: 35676740
DOI: 10.1186/s13071-022-05284-w -
Trends in Parasitology Jan 2018Parasitic nematodes are biomedically and economically important, but many are genetically intractable which limits our understanding of their molecular and cellular...
Parasitic nematodes are biomedically and economically important, but many are genetically intractable which limits our understanding of their molecular and cellular biology. Gang et al. report CRISPR/Cas9 genome editing in parasites of the genus Strongyloides, generating both knock-outs and knock-ins, and demonstrated heritability of the modifications, a crucial advance in the field.
Topics: Animals; Clustered Regularly Interspaced Short Palindromic Repeats; Gene Editing; Strongyloides
PubMed: 29174224
DOI: 10.1016/j.pt.2017.11.005