Pathogens

2023

Jump to: 2022, 2021

5 pages, 225 KiB

Open AccessOpinion

Pathogenesis of Cerebral Malaria: New Trends and Insights for Developing Adjunctive Therapies

by Praveen Kishore Sahu and Sanjib Mohanty

Pathogens 2023, 12(4), 522; https://doi.org/10.3390/pathogens12040522 - 27 Mar 2023

Cited by 3 | Viewed by 2399

Abstract

No specific or adjunctive therapies exist to treat cerebral malaria (CM) as of date. CM is a neuropathological manifestation of the malaria infection in humans, caused by the hemoparasitic pathogen Plasmodium falciparum. Driven through a multitude of virulence factors, varied immune responses, [...] Read more.

No specific or adjunctive therapies exist to treat cerebral malaria (CM) as of date. CM is a neuropathological manifestation of the malaria infection in humans, caused by the hemoparasitic pathogen Plasmodium falciparum. Driven through a multitude of virulence factors, varied immune responses, variations in brain swelling with regard to the age of patients, parasite biomass, and parasite-typing, the essential pathogenetic mechanisms underlying clinical CM have remained elusive. However, a recent series of studies based on molecular, immunologic, and advanced neuroradiologic and machine-learning approaches have unraveled new trends and insights to better understand and focus on the key determinants of CM in humans. This could possibly be the beginning of the design of new and effective adjunctive therapies that may not be common or applicable to the entire malarious world, but that could, rather, be specific to the variations in the determinants of CM. Full article

8 pages, 724 KiB

Open AccessOpinion

Subspecific Nomenclature of Giardia duodenalis in the Light of a Compared Population Genomics of Pathogens

by Michel Tibayrenc

Pathogens 2023, 12(2), 249; https://doi.org/10.3390/pathogens12020249 - 3 Feb 2023

Cited by 1 | Viewed by 1478

Abstract

Genetic and genomic data have long recognized that the species Giardia duodenalis is subdivided into at least eight genetic clusters that have been named “assemblages” by specialists in the field. Some of these assemblages have been given the status of species, with Linnean [...] Read more.

Genetic and genomic data have long recognized that the species Giardia duodenalis is subdivided into at least eight genetic clusters that have been named “assemblages” by specialists in the field. Some of these assemblages have been given the status of species, with Linnean binames. In the framework of the predominant clonal evolution model (PCE), we have shown that, from an evolutionary point of view, G. duodenalis assemblages are equatable to “near-clades”, that is to say: clades whose discreteness is somewhat clouded by occasional genetic exchange, but remain discrete and stable in space and time. The implications of this evolutionary status for the species described within G. duodenalis are discussed in light of the most recent genetic and genomic studies. The pattern of this species’ subspecific genetic variability and genetic clustering appears to be very similar to the ones of various parasitic, fungal and bacteria species. This underlines the relevance of a compared population genomics of pathogenic species allowed by the broad framework of the PCE model. Full article

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2022

Jump to: 2023, 2021

13 pages, 4741 KiB

Open AccessArticle

Sugar Coating: Utilisation of Host Serum Sialoglycoproteins by Schistosoma mansoni as a Potential Immune Evasion Mechanism

by Maude Dagenais, Jared Q. Gerlach, Timothy G. Geary and Thavy Long

Pathogens 2022, 11(4), 426; https://doi.org/10.3390/pathogens11040426 - 31 Mar 2022

Cited by 4 | Viewed by 2973

Abstract

Parasitic helminths resort to various mechanisms to evade and modulate their host’s immune response, several of which have been described for Schistosoma mansoni. We recently reported the presence of sialic acid residues on the surface of adult S. mansoni extracellular vesicles (EVs). [...] Read more.

Parasitic helminths resort to various mechanisms to evade and modulate their host’s immune response, several of which have been described for Schistosoma mansoni. We recently reported the presence of sialic acid residues on the surface of adult S. mansoni extracellular vesicles (EVs). We now report that these sialylated molecules are mammalian serum proteins. In addition, our data suggest that most sialylated EV-associated proteins do not elicit a humoral response upon injection into mice, or in sera obtained from infected animals. Sialic acids frequently terminate glycans on the surface of vertebrate cells, where they serve important functions in physiological processes such as cell adhesion and signalling. Interestingly, several pathogens have evolved ways to mimic or utilise host sialic acid beneficially by coating their own proteins, thereby facilitating cell invasion and providing protection from host immune effectors. Together, our results indicate that S. mansoni EVs are coated with host glycoproteins, which may contribute to immune evasion by masking antigenic sites, protecting EVs from removal from serum and aiding in cell adhesion and entry to exert their functions. Full article

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2021

Jump to: 2023, 2022

12 pages, 2194 KiB

Open AccessEditor’s ChoiceArticle

Pb103 Regulates Zygote/Ookinete Development in Plasmodium berghei via Double Zinc Finger Domains

by Makoto Hirai, Akimasa Maeta, Toshiyuki Mori and Toshihiro Mita

Pathogens 2021, 10(12), 1536; https://doi.org/10.3390/pathogens10121536 - 24 Nov 2021

Cited by 4 | Viewed by 2627

Abstract

Sexual reproduction of Plasmodium parasites takes place in anopheline mosquitoes, where male and female gametes fuse to form zygotes and then ookinetes. These processes are orchestrated by stage-specific protein expression, which is mediated in part by translational repression. Accumulating evidence shows that RNA [...] Read more.

Sexual reproduction of Plasmodium parasites takes place in anopheline mosquitoes, where male and female gametes fuse to form zygotes and then ookinetes. These processes are orchestrated by stage-specific protein expression, which is mediated in part by translational repression. Accumulating evidence shows that RNA binding proteins (RBPs) play crucial roles in these processes. Here, we report the characterization of P. berghei 103 (Pb103), which encodes a protein possessing double zinc finger domains (ZFs), an RBP. Reporter parasites expressing azami green fluorescent protein (AGFP) under the endogenous Pb103 gene promoter (Pb103-AGFP reporter) showed that the AGFP fluorescent signal was detected from gametes to ookinetes, while AGFP mRNA was translationally repressed in female gametocytes. The Pb103-disrupted parasites (Pb103(−)) grew and produced gametocytes with similar efficiencies to those of wild-type parasites. However, no oocysts were formed in mosquitoes fed Pb103(−). An in vitro fertilization assay showed abortion at the zygote stage in Pb103(−), suggesting that Pb103 plays a critical role in zygote/ookinete development. Cross-fertilization assays with Pb103(−) and male- or female-sterile parasites revealed that Pb103 was essential exclusively for female gametes. To identify the domains critical for zygote/ookinete development, transgenic parasites expressing partially deleted Pb103 were generated and assayed for ookinete maturation. As a result, deleting either of two ZFs but not the C-terminal region abolished zygote/ookinete development, highlighting the indispensable roles of ZFs in parasite sexual development, most likely via translational repression. Full article

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19 pages, 29662 KiB

Open AccessArticle

Artemisinin Binds and Inhibits the Activity of Plasmodium falciparum Ddi1, a Retroviral Aspartyl Protease

by Noah Machuki Onchieku, Sonam Kumari, Rajan Pandey, Vaibhav Sharma, Mohit Kumar, Arunaditya Deshmukh, Inderjeet Kaur, Asif Mohmmed, Dinesh Gupta, Daniel Kiboi, Naseem Gaur and Pawan Malhotra

Pathogens 2021, 10(11), 1465; https://doi.org/10.3390/pathogens10111465 - 11 Nov 2021

Cited by 6 | Viewed by 3968

Abstract

Reduced sensitivity of the human malaria parasite, Plasmodium falciparum, to Artemisinin and its derivatives (ARTs) threatens the global efforts towards eliminating malaria. ARTs have been shown to cause ubiquitous cellular and genetic insults, which results in the activation of the unfolded protein response [...] Read more.

Reduced sensitivity of the human malaria parasite, Plasmodium falciparum, to Artemisinin and its derivatives (ARTs) threatens the global efforts towards eliminating malaria. ARTs have been shown to cause ubiquitous cellular and genetic insults, which results in the activation of the unfolded protein response (UPR) pathways. The UPR restores protein homeostasis, which otherwise would be toxic to cellular survival. Here, we interrogated the role of DNA-damage inducible protein 1 (PfDdi1), a unique proteasome-interacting retropepsin in mediating the actions of the ARTs. We demonstrate that PfDdi1 is an active A₂ family protease that hydrolyzes ubiquitinated proteasome substrates. Treatment of P. falciparum parasites with ARTs leads to the accumulation of ubiquitinated proteins in the parasites and blocks the destruction of ubiquitinated proteins by inhibiting the PfDdi1 protease activity. Besides, whereas the PfDdi1 is predominantly localized in the cytoplasm, exposure of the parasites to ARTs leads to DNA fragmentation and increased recruitment of the PfDdi1 into the nucleus. Furthermore, we show that Ddi1 knock-out Saccharomycescerevisiae cells are more susceptible to ARTs and the PfDdI1 protein robustly restores the corresponding functions in the knock-out cells. Together, these results show that ARTs act in multiple ways; by inducing DNA and protein damage and might be impairing the damage recovery by inhibiting the activity of PfDdi1, an essential ubiquitin-proteasome retropepsin. Full article

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15 pages, 6625 KiB

Open AccessArticle

Analysis of Schistosoma mansoni Extracellular Vesicles Surface Glycans Reveals Potential Immune Evasion Mechanism and New Insights on Their Origins of Biogenesis

by Maude Dagenais, Jared Q. Gerlach, George R. Wendt, James J. Collins III, Louise E. Atkinson, Angela Mousley, Timothy G. Geary and Thavy Long

Pathogens 2021, 10(11), 1401; https://doi.org/10.3390/pathogens10111401 - 29 Oct 2021

Cited by 10 | Viewed by 3527

Abstract

Parasitic helminths are master manipulators of host immunity. Their strategy is complex and involves the release of excreted/secreted products, including extracellular vesicles (EVs). The protein and miRNA contents of EVs have been characterised for many parasitic helminths but, despite reports suggesting the importance [...] Read more.

Parasitic helminths are master manipulators of host immunity. Their strategy is complex and involves the release of excreted/secreted products, including extracellular vesicles (EVs). The protein and miRNA contents of EVs have been characterised for many parasitic helminths but, despite reports suggesting the importance of EV surface carbohydrate structures (glycans) in the interactions with target cells and thus subsequent effector functions, little is known about parasite EV glycomics. Using lectin microarrays, we identified several lectins that exhibit strong adhesion to Schistosoma mansoni EVs, suggesting the presence of multiple glycan structures on these vesicles. Interestingly, SNA-I, a lectin that recognises structures with terminal sialic acid, displayed strong affinity for S. mansoni EVs, which was completely abolished by neuraminidase treatment, suggesting sialylation in the EV sample. This finding is of interest, as sialic acids play important roles in the context of infection by aiding immune evasion, affecting target recognition, cell entry, etc., but are not thought to be synthesised by helminths. These data were validated by quantitative analysis of free sialic acid released from EVs following treatment with neuraminidase. Lectin histochemistry and fluorescence in situ hybridisation analyses on whole adult worms suggest the involvement of sub-tegumental cell bodies, as well as the digestive and excretory systems, in the release of EVs. These results support previous reports of EV biogenesis diversity in trematodes and potentially highlight new means of immune modulation and evasion employed by schistosomes. Full article

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19 pages, 1330 KiB

Open AccessReview

Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases

by Darine Daher, Ahmad Shaghlil, Eyad Sobh, Maguy Hamie, Malika Elhage Hassan, Mohamad Bahij Moumneh, Shaymaa Itani, Rana El Hajj, Lina Tawk, Marwan El Sabban and Hiba El Hajj

Pathogens 2021, 10(11), 1351; https://doi.org/10.3390/pathogens10111351 - 20 Oct 2021

Cited by 49 | Viewed by 13342

Abstract

Toxoplasma gondii (T. gondii) is a prevalent protozoan parasite of medical and veterinary significance. It is the etiologic agent of toxoplasmosis, a neglected disease in which incidence and symptoms differ between patients and regions. In immunocompetent patients, toxoplasmosis manifests as acute [...] Read more.

Toxoplasma gondii (T. gondii) is a prevalent protozoan parasite of medical and veterinary significance. It is the etiologic agent of toxoplasmosis, a neglected disease in which incidence and symptoms differ between patients and regions. In immunocompetent patients, toxoplasmosis manifests as acute and chronic forms. Acute toxoplasmosis presents as mild or asymptomatic disease that evolves, under the host immune response, into a persistent chronic disease in healthy individuals. Chronic toxoplasmosis establishes as latent tissue cysts in the brain and skeletal muscles. In immunocompromised patients, chronic toxoplasmosis may reactivate, leading to a potentially life-threatening condition. Recently, the association between toxoplasmosis and various diseases has been shown. These span primary neuropathies, behavioral and psychiatric disorders, and different types of cancer. Currently, a direct pre-clinical or clinical molecular connotation between toxoplasmosis and most of its associated diseases remains poorly understood. In this review, we provide a comprehensive overview on Toxoplasma-induced and associated diseases with a focus on available knowledge of the molecular players dictating these associations. We will also abridge the existing therapeutic options of toxoplasmosis and highlight the current gaps to explore the implications of toxoplasmosis on its associated diseases to advance treatment modalities. Full article

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17 pages, 1149 KiB

Open AccessArticle

Molecular Epidemiology of G6PD Genotypes in Different Ethnic Groups Residing in Saharan and Sahelian Zones of Mauritania

by Oum Kelthoum Mamadou Djigo, Mohamed Salem Ould Ahmedou Salem, Sileye Mamadou Diallo, Mohamed Abdallahi Bollahi, Boushab Mohamed Boushab, Aymeric Garre, Nasserdine Papa Mze, Leonardo Basco, Sébastien Briolant and Ali Ould Mohamed Salem Boukhary

Pathogens 2021, 10(8), 931; https://doi.org/10.3390/pathogens10080931 - 23 Jul 2021

Cited by 6 | Viewed by 4366

Abstract

Plasmodium vivax malaria is endemic in Mauritania. Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may develop acute hemolytic anemia when exposed to 8-aminoquinoline antimalarial drugs, which are indispensable for a complete cure. The prevalence of G6PD allelic variants was assessed in different ethno-linguistic groups [...] Read more.

Plasmodium vivax malaria is endemic in Mauritania. Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency may develop acute hemolytic anemia when exposed to 8-aminoquinoline antimalarial drugs, which are indispensable for a complete cure. The prevalence of G6PD allelic variants was assessed in different ethno-linguistic groups present in Mauritania. A total of 996 blood samples (447 males and 549 females; 499 white Moors and 497 individuals of black African ancestry) were collected from febrile patients in 6 different study sites: Aleg, Atar, Kiffa, Kobeni, Nouakchott, and Rosso. The presence of the African-type G6PD A- (G202A, A376G, A542T, G680T, and T968C mutations) and the Mediterranean-type G6PD B- (C563T) variants was assessed by PCR followed by restriction fragment length polymorphism and/or DNA sequencing. The prevalence of African-type G6PD A- genotype was 3.6% (36/996), with 6.3% (28/447) of hemizygote (A-) males and 1.5% (8/549) of homozygous (A-A-) females. Forty of 549 (7.3%) women were heterozygous (AA-). The following genotypes were observed among hemizygous men and/or homozygous women: A376G/G202A (22/996; 2.2%), A376G/T968C Betica-Selma (12/996; 1.2%), and A376G/A542T Santamaria (2/996; 0.2%). The Mediterranean-type G6PD B- genotype was not observed. The prevalence rates of G6PD A- genotype in male (10/243; 4.1%) and heterozygous female (6/256; 2.3%) white Moors were lower (p < 0.05) than those of males (18/204; 8.8%) and heterozygous females (34/293; 11.6%) of black African ancestry. There were only a few homozygous women among both white Moors (3/256; 1.2%) and those of black African ancestry (5/293; 1.7%). The prevalence of G6PD deficiency in Mauritania was comparable to that of neighboring countries in the Maghreb. Because of the purportedly close ethnic ties between the Mauritanian white Moors and the peoples in the Maghreb, further investigations on the possible existence of the Mediterranean-type allele are required. Moreover, a surveillance system of G6PD phenotype and/or genotype screening is warranted to establish and monitor a population-based prevalence of G6PD deficiency. Full article

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12 pages, 2497 KiB

Open AccessArticle

First Molecular Characterization of Cryptosporidium spp. in Patients Living with HIV in Honduras

by Sergio Betancourth, Osman Archaga, Wendy Moncada, Vilma Rodríguez and Gustavo Fontecha

Pathogens 2021, 10(3), 336; https://doi.org/10.3390/pathogens10030336 - 13 Mar 2021

Cited by 2 | Viewed by 3532

Abstract

Cryptosporidiosis is one of the most important causes of gastroenteritis in the world, especially in low- and middle-income countries. It is caused by the Apicomplexan parasite Cryptosporidium spp., and mainly affects children and immunocompromised people, in whom it can pose a serious threat [...] Read more.

Cryptosporidiosis is one of the most important causes of gastroenteritis in the world, especially in low- and middle-income countries. It is caused by the Apicomplexan parasite Cryptosporidium spp., and mainly affects children and immunocompromised people, in whom it can pose a serious threat to their health, or even be life threatening. In Honduras, there are no data on parasite species or on molecular diversity or Cryptosporidium subtypes. Therefore, a cross-sectional study was conducted between September 2019 and March 2020 for the molecular identification of Cryptosporidium spp. in 102 patients living with HIV who attended a national hospital in Tegucigalpa. Stool samples were analyzed by direct microscopy, acid-fast stained smears, and a rapid lateral flow immunochromatographic test. All samples that tested positive were molecularly analyzed to identify the species and subtype of the parasite using three different markers: gp60, cowp, and 18Sr. PCR products were also sequenced. Four out of 102 samples (3.92%) were positive for Cryptosporidiumparvum, and all were assigned to subtype IIa. These findings suggest a possible zoonotic transmission in this population. Full article

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2023

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