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Cell Genomics May 2024Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms are often part of diverse and...
Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms are often part of diverse and highly mutable gene families. Even in this context, we discovered unprecedented variation in the hyper-variable (HYP) effectors of plant-parasitic nematodes. HYP effectors are single-gene loci that potentially harbor thousands of alleles. Alleles vary in the organization, as well as the number, of motifs within a central hyper-variable domain (HVD). We dramatically expand the HYP repertoire of two plant-parasitic nematodes and define distinct species-specific "rules" underlying the apparently flawless genetic rearrangements. Finally, by analyzing the HYPs in 68 individual nematodes, we unexpectedly found that despite the huge number of alleles, most individuals are germline homozygous. These data support a mechanism of programmed genetic variation, termed HVD editing, where alterations are locus specific, strictly governed by rules, and theoretically produce thousands of variants without errors.
PubMed: 38815588
DOI: 10.1016/j.xgen.2024.100580 -
PLoS Pathogens May 2024The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg "winners" attach to...
The eggs of the blood fluke Schistosoma mansoni are the main cause of the clinical manifestations of chronic schistosomiasis. After laying, the egg "winners" attach to the endothelium of the mesenteric vein and, after a period of development, induce the growth of a small granuloma, which facilitates their passage to the intestinal lumen. Egg "losers" carried by the bloodstream to non-specific tissues also undergo full development and induce large granuloma formation, but their life ends there. Although these trapped eggs represent a dead end in the parasite life cycle, the vast majority of studies attempting to describe the biology of the S. mansoni eggs have studied these liver-trapped "losers" instead of migrating intestinal "winners". This raises the fundamental question of how these eggs differ. With robust comparative transcriptomic analysis performed on S. mansoni eggs isolated 7 weeks post infection, we show that gene expression is critically dependent on tissue localization, both in the early and late stages of development. While mitochondrial genes and venom allergen-like proteins are significantly upregulated in mature intestinal eggs, well-described egg immunomodulators IPSE/alpha-1 and omega-1, together with micro-exon genes, are predominantly expressed in liver eggs. In addition, several proteases and protease inhibitors previously implicated in egg-host interactions display clear tissue-specific gene expression patterns. These major differences in gene expression could be then reflected in the observed different ability of liver and intestinal soluble egg antigens to elicit host immune responses and in the shorter viability of miracidia hatched from liver eggs. Our comparative analysis provides a new perspective on the biology of parasite's eggs in the context of their development and tissue localization. These findings could contribute to a broader and more accurate understanding of parasite eggs interactions with the host, which have historically been often restricted to liver eggs and sometimes inaccurately generalized.
PubMed: 38814989
DOI: 10.1371/journal.ppat.1012268 -
PLoS Pathogens May 2024Toxoplasma gondii is a foodborne pathogen that can cause severe and life-threatening infections in fetuses and immunocompromised patients. Felids are its only definitive...
Toxoplasma gondii is a foodborne pathogen that can cause severe and life-threatening infections in fetuses and immunocompromised patients. Felids are its only definitive hosts, and a wide range of animals, including humans, serve as intermediate hosts. When the transmissible bradyzoite stage is orally ingested by felids, they transform into merozoites that expand asexually, ultimately generating millions of gametes for the parasite sexual cycle. However, bradyzoites in intermediate hosts differentiate exclusively to disease-causing tachyzoites, which rapidly disseminate throughout the host. Though tachyzoites are well-studied, the molecular mechanisms governing transitioning between developmental stages are poorly understood. Each parasite stage can be distinguished by a characteristic transcriptional signature, with one signature being repressed during the other stages. Switching between stages require substantial changes in the proteome, which is achieved in part by ubiquitination. F-box proteins mediate protein poly-ubiquitination by recruiting substrates to SKP1, Cullin-1, F-Box protein E3 ubiquitin ligase (SCF-E3) complexes. We have identified an F-box protein named Toxoplasma gondii F-Box Protein L2 (TgFBXL2), which localizes to distinct perinucleolar sites. TgFBXL2 is stably engaged in an SCF-E3 complex that is surprisingly also associated with a COP9 signalosome complex that negatively regulates SCF-E3 function. At the cellular level, TgFBXL2-depleted parasites are severely defective in centrosome replication and daughter cell development. Most remarkable, RNAseq data show that TgFBXL2 conditional depletion induces the expression of stage-specific genes including a a large cohort of genes necessary for sexual commitment. Together, these data suggest that TgFBXL2 is a latent guardian of stage specific gene expression in Toxoplasma and poised to remove conflicting proteins in response to an unknown trigger of development.
PubMed: 38814984
DOI: 10.1371/journal.ppat.1012269 -
PLoS Neglected Tropical Diseases May 2024
Topics: Leishmania tropica; Animals; Phlebotomus; Salivary Proteins and Peptides; Plasmids; Insect Proteins; Mice; Humans; Leishmaniasis, Cutaneous; Female
PubMed: 38814961
DOI: 10.1371/journal.pntd.0012218 -
PloS One 2024Opisthorchis viverrini (O. viverrini, Ov) infection and consumption of high-fat and high-fructose (HFF) diet exacerbate liver and kidney disease. Here, we investigated...
BACKGROUND
Opisthorchis viverrini (O. viverrini, Ov) infection and consumption of high-fat and high-fructose (HFF) diet exacerbate liver and kidney disease. Here, we investigated the effects of a combination of O. viverrini infection and HFF diet on kidney pathology via changes in the gut microbiome and host proteome in hamsters.
METHODOLOGY/PRINCIPAL FINDINGS
Twenty animals were divided into four groups; 1) fed a normal diet not infected with O. viverrini (normal group), 2) fed an HFF diet and not infected with O. viverrini (HFF), 3) fed a normal diet and infected with O. viverrini (Ov), and 4) fed an HFF diet and infected with O. viverrini (HFFOv). DNA was extracted from fecal samples and the V3-V4 region of the bacterial 16S rRNA gene sequenced on an Illumina MiSeq sequencing platform. In addition, LC/MS-MS analysis was done. Histopathological studies and biochemical assays were also conducted. The results indicated that the HFFOv group exhibited the most severe kidney injury, manifested as elevated KIM-1 expression and accumulation of fibrosis in kidney tissue. The microbiome of the HFFOv group was more diverse than in the HFF group: there were increased numbers of Ruminococcaceae, Lachnospiraceae, Desulfovibrionaceae and Akkermansiaceae, but fewer Eggerthellaceae. In total, 243 host proteins were identified across all groups. Analysis using STITCH predicted that host proteome changes may lead to leaking of the gut, allowing molecules such as soluble CD14 and p-cresol to pass through to promote kidney disease. In addition, differential expression of TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 (Tab2, involving renal inflammation and injury) are predicted to be associated with kidney disease.
CONCLUSIONS/SIGNIFICANCE
The combination of HFF diet and O. viverrini infection may promote kidney injury through alterations in the gut microbiome and host proteome. This knowledge may suggest an effective strategy to prevent kidney disease beyond the early stages.
Topics: Animals; Fructose; Opisthorchiasis; Diet, High-Fat; Metagenomics; Cricetinae; Proteomics; Gastrointestinal Microbiome; Kidney Diseases; Opisthorchis; Male; Proteome; Kidney; Mesocricetus; RNA, Ribosomal, 16S
PubMed: 38814931
DOI: 10.1371/journal.pone.0301907 -
PLoS Neglected Tropical Diseases May 2024Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver...
Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver and lungs. Although the heart is affected in only 0.02-2% of all CE cases, a considerable number of cases have been, and continue to be, published. However, due to the rare occurrence of cardiac CE and the resulting lack of clinical trials, knowledge about various aspects of the disease remains limited. To obtain a clearer picture of anatomical, clinical, diagnostic as well as therapeutic aspects of cardiac CE, we systematically reviewed the literature published between 1965 and 2022. The anatomical pattern of the affected cardiac structures follows the extension of the supplying capillary bed. The majority of patients (82.7%) are symptomatic and present with prolonged non-specific symptoms such as dyspnoea, chest pain and palpitations. Acute complications generally derive from cyst rupture, occur in 18.3% of cases and manifest as embolism, pericardial tamponade, or anaphylactic reaction in 83.2%, 17.8% and 10.9% of these cases, respectively. As for CE cysts localized in other organs, the diagnosis of cardiac CE is made by imaging. Serology plays a minor role due to its limited sensitivity. Unlike abdominal CE cysts, cardiac CE cysts are usually resected independent of their stage (active/inactive), because their presence impairs cardiac performance and carries the risk of long-term sequelae. More than 80% of patients are treated with a single surgical intervention. We found a disease-related case fatality rate of 11.1%. Since local recurrence was reported up to 108 months and secondary CE up to 72 months after surgery, patients should be followed up for a minimum of 10 years.
Topics: Humans; Echinococcosis; Animals; Heart Diseases; Echinococcus granulosus; Heart
PubMed: 38814859
DOI: 10.1371/journal.pntd.0012183 -
Cell Reports May 2024The protozoan parasite Cryptosporidium is a leading cause of diarrhea in young children. The parasite's life cycle involves a coordinated and timely progression from...
The protozoan parasite Cryptosporidium is a leading cause of diarrhea in young children. The parasite's life cycle involves a coordinated and timely progression from asexual to sexual stages, leading to the formation of the transmissible oocyst. Underlying molecular signaling mechanisms orchestrating sexual development are not known. Here, we describe the function of a signaling kinase in Cryptosporidium male gametogenesis. We reveal the expression of Cryptosporidium parvum calcium-dependent protein kinase 5 (CDPK5) during male gamete development and its important role in the egress of mature gametes. Genetic ablation of this kinase results in viable parasites, indicating that this gene is dispensable for parasite survival. Interestingly, cdpk5 deletion decreases parasite virulence and impacts oocyst shedding in immunocompromised mice. Using phosphoproteomics, we identify possible CDPK5 substrates and biological processes regulated by this kinase. Collectively, these findings illuminate parasite cell biology by revealing a mechanism controlling male gamete production and a potential target to block disease transmission.
PubMed: 38814783
DOI: 10.1016/j.celrep.2024.114263 -
Veterinary Medicine and Science Jul 2024Eimeria is a protozoan parasite that affects poultry, particularly chickens, causing a disease known as coccidiosis. This disease imposes substantial significant... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eimeria is a protozoan parasite that affects poultry, particularly chickens, causing a disease known as coccidiosis. This disease imposes substantial significant economic challenges to the poultry sector.
OBJECTIVES
The current study aimed to estimate the global prevalence and associated risk factors of Eimeria in domestic chickens.
METHODS
Multiple databases (Scopus, PubMed, ProQuest, Web of Science and Google Scholar) were searched for articles published until June 2023. The pooled prevalence was estimated using a random-effects model with a 95% confidence interval. The statistical analysis was conducted using meta packages in R version (3.6.1).
RESULTS
In total, 41 articles fulfilled the eligibility criteria. The global pooled prevalence was 44.3% (36.9%-51.8%) with Eimeria tenella (38.7%, 30.1%-47.7%) as the most prevalent species. The highest pooled prevalence was related to the Western Pacific Region (80.5%, 72.6%-87.3%) and urban areas (44.4%, 36.5%-52.6%). Moreover, areas with humid subtropical climates represent the highest overall prevalence (75.8%, 46.6%-95.9%).
CONCLUSION
The necessity for robust and innovative strategies for preventing and managing this disease cannot be overstated. Addressing Eimeria impact is crucial not only for safeguarding poultry health but also for sustaining the economic viability of the poultry industry.
Topics: Animals; Chickens; Coccidiosis; Poultry Diseases; Prevalence; Eimeria; Risk Factors; Global Health
PubMed: 38814576
DOI: 10.1002/vms3.1469 -
Folia Parasitologica Apr 2024Coccidiosis is a protozoan intestinal disease that reduces the production of the sheep industry and causes large economic losses for sheep. Although chemically...
Coccidiosis is a protozoan intestinal disease that reduces the production of the sheep industry and causes large economic losses for sheep. Although chemically synthesised drugs are routinely employed to treat coccidiosis in sheep, the anticoccidial drug resistance and drug residues in edible meat have prompted an urgent search for alternatives. Herein, the anticoccidial properties of diclazuril, a conventional anticoccidial drug, and Allium sativum, Houttuynia cordata and Portulaca oleracea were assessed. Forty 45-day-old lambs naturally infected with Eimeria spp. were selected and randomly divided into five groups. The results showed that the sheep treated for coccidiosis had considerably decreased average daily gain (ADG) during both administration and withdrawal of the drug compared to the control group. Furthermore, at days 14, 21, 28 and 35, respectively, the three herbs and diclazuril had similar anticoccidial effects, with lower oocysts per gram (OPG) than the control group. On day 78, OPG in the three herbal groups was significantly lower than in the diclazuril group. In addition, the abundance and composition of the gut microbiota were changed in sheep treated with the three herbs and diclazuril compared to the untreated sheep. Moreover, some intestinal microorganisms have a correlation with OPG and ADG when using Spearman correlation analysis. In summary, our results suggest that all three herbs produce anticoccidial effects similar to diclazuril and modulate the balance of gut microbiota in growing lambs.
Topics: Animals; Coccidiosis; Gastrointestinal Microbiome; Sheep; Sheep Diseases; Drugs, Chinese Herbal; Oocysts; Coccidiostats; Eimeria; Triazines
PubMed: 38813809
DOI: 10.14411/fp.2024.009 -
Turkish Journal of Medical Sciences 2023Human Demodex mites are parasites that live in the pilosebaceous unit and can cause demodicosis. While demodicosis may occur as a primary skin disease, it may also...
BACKGROUND/AIM
Human Demodex mites are parasites that live in the pilosebaceous unit and can cause demodicosis. While demodicosis may occur as a primary skin disease, it may also result from immunosuppression and topical or systemic immunosuppressive therapies. Surgical rhinoplasty is one of the most commonly performed cosmetic procedures, and it is the cause of a variety of cutaneous complications, particularly acne, as it affects the skin's adnexal structures. Thus, this study aimed to investigate whether the cutaneous changes in surgical rhinoplasty patients render them vulnerable to Demodex infestation.
MATERIALS AND METHODS
Individuals who had undergone rhinoplasty (patients) and age- and sex-matched healthy volunteers (controls) were included in this prospective case-control study. To determine the Demodex density, samples were collected from the malar and nasal regions of both the patients and controls using the standard superficial skin biopsy method.
RESULTS
A total of 50 rhinoplasty patients and 50 healthy controls were enrolled in the study. The Demodex density on the nose was significantly higher in the rhinoplasty patients (p = 0.0001). Furthermore, the frequency of xerosis and pustules was significantly higher in the rhinoplasty patients compared to the control group (p = 0.046 and p = 0.001, respectively).
CONCLUSION
Surgical rhinoplasty may be a risk factor for demodicosis, and patients will recover faster after surgery with proper diagnosis and treatment.
Topics: Humans; Rhinoplasty; Mite Infestations; Case-Control Studies; Male; Female; Adult; Prospective Studies; Animals; Mites; Young Adult; Middle Aged
PubMed: 38813499
DOI: 10.55730/1300-0144.5743