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How colonization bottlenecks, tissue niches, and transmission strategies shape protozoan infections.Trends in Parasitology Dec 2023Protozoan pathogens such as Plasmodium spp., Leishmania spp., Toxoplasma gondii, and Trypanosoma spp. are often associated with high-mortality, acute and chronic... (Review)
Review
Protozoan pathogens such as Plasmodium spp., Leishmania spp., Toxoplasma gondii, and Trypanosoma spp. are often associated with high-mortality, acute and chronic diseases of global health concern. For transmission and immune evasion, protozoans have evolved diverse strategies to interact with a range of host tissue environments. These interactions are linked to disease pathology, yet our understanding of the association between parasite colonization and host homeostatic disruption is limited. Recently developed techniques for cellular barcoding have the potential to uncover the biology regulating parasite transmission, dissemination, and the stability of infection. Understanding bottlenecks to infection and the in vivo tissue niches that facilitate chronic infection and spread has the potential to reveal new aspects of parasite biology.
Topics: Animals; Humans; Host-Parasite Interactions; Protozoan Infections; Parasites; Toxoplasma; Plasmodium
PubMed: 37839913
DOI: 10.1016/j.pt.2023.09.017 -
Genes Feb 2024Ion channels serve many cellular functions including ion homeostasis, volume regulation, signaling, nutrient acquisition, and developmental progression. Although the... (Review)
Review
Ion channels serve many cellular functions including ion homeostasis, volume regulation, signaling, nutrient acquisition, and developmental progression. Although the complex life cycles of malaria parasites necessitate ion and solute flux across membranes, the whole-genome sequencing of the human pathogen revealed remarkably few orthologs of known ion channel genes. Contrasting with this, biochemical studies have implicated the channel-mediated flux of ions and nutritive solutes across several membranes in infected erythrocytes. Here, I review advances in the cellular and molecular biology of ion channels in malaria parasites. These studies have implicated novel parasite genes in the formation of at least two ion channels, with additional ion channels likely present in various membranes and parasite stages. Computational approaches that rely on homology to known channel genes from higher organisms will not be very helpful in identifying the molecular determinants of these activities. Given their unusual properties, novel molecular and structural features, and essential roles in pathogen survival and development, parasite channels should be promising targets for therapy development.
Topics: Animals; Humans; Parasites; Ion Channels; Plasmodium falciparum; Ions; Malaria
PubMed: 38540355
DOI: 10.3390/genes15030296 -
PLoS Pathogens Jul 2023A key element of Plasmodium biology and pathogenesis is the trafficking of ~10% of the parasite proteome into the host red blood cell (RBC) it infects. To cross the...
A key element of Plasmodium biology and pathogenesis is the trafficking of ~10% of the parasite proteome into the host red blood cell (RBC) it infects. To cross the parasite-encasing parasitophorous vacuole membrane, exported proteins utilise a channel-forming protein complex termed the Plasmodium translocon of exported proteins (PTEX). PTEX is obligatory for parasite survival, both in vitro and in vivo, suggesting that at least some exported proteins have essential metabolic functions. However, to date only one essential PTEX-dependent process, the new permeability pathways, has been described. To identify other essential PTEX-dependant proteins/processes, we conditionally knocked down the expression of one of its core components, PTEX150, and examined which pathways were affected. Surprisingly, the food vacuole mediated process of haemoglobin (Hb) digestion was substantially perturbed by PTEX150 knockdown. Using a range of transgenic parasite lines and approaches, we show that two major Hb proteases; falcipain 2a and plasmepsin II, interact with PTEX core components, implicating the translocon in the trafficking of Hb proteases. We propose a model where these proteases are translocated into the PV via PTEX in order to reach the cytostome, located at the parasite periphery, prior to food vacuole entry. This work offers a second mechanistic explanation for why PTEX function is essential for growth of the parasite within its host RBC.
Topics: Animals; Plasmodium falciparum; Vacuoles; Protein Transport; Protozoan Proteins; Erythrocytes; Parasites; Peptide Hydrolases
PubMed: 37523385
DOI: 10.1371/journal.ppat.1011006 -
Trends in Parasitology Jul 2023The human malaria parasites, including Plasmodium falciparum, persist as a major cause of global morbidity and mortality. The recent stalling of progress toward malaria... (Review)
Review
The human malaria parasites, including Plasmodium falciparum, persist as a major cause of global morbidity and mortality. The recent stalling of progress toward malaria elimination substantiates a need for novel interventions. Controlled gene expression is central to the parasite's numerous life cycle transformations and adaptation. With few specific transcription factors (TFs) identified, crucial roles for chromatin states and epigenetics in parasite transcription have become evident. Although many chromatin-modifying enzymes are known, less is known about which factors mediate their impacts on transcriptional variation. Like those of higher eukaryotes, long noncoding RNAs (lncRNAs) have recently been shown to have integral roles in parasite gene regulation. This review aims to summarize recent developments and key findings on the role of lncRNAs in P. falciparum.
Topics: Animals; Humans; Parasites; RNA, Long Noncoding; Gene Expression Regulation; Malaria, Falciparum; Chromatin; Plasmodium falciparum; Malaria
PubMed: 37121862
DOI: 10.1016/j.pt.2023.03.016 -
Frontiers in Cellular and Infection... 2024
Topics: Animals; Parasites; Host-Parasite Interactions
PubMed: 38638829
DOI: 10.3389/fcimb.2024.1391289 -
Trends in Parasitology Dec 2023With growing human populations living along freshwater shores and marine coastlines, aquatic ecosystems are experiencing rising levels of light pollution. Through its... (Review)
Review
With growing human populations living along freshwater shores and marine coastlines, aquatic ecosystems are experiencing rising levels of light pollution. Through its effects on hosts and parasites, anthropogenic light at night can disrupt host-parasite interactions evolved under a normal photoperiod. Yet its impact on aquatic parasites has been ignored to date. Here, I discuss the direct effects of light on the physiology and behaviour of parasite infective stages and their hosts. I argue that night-time lights can change the spatiotemporal dynamics of infection risk and drive the rapid evolution of parasites. I then highlight knowledge gaps and how impacts on parasitic diseases should be incorporated into the design of measures aimed at mitigating the impact of anthropogenic light on wildlife.
Topics: Animals; Humans; Host-Parasite Interactions; Ecosystem; Light Pollution; Parasites; Animals, Wild
PubMed: 37722935
DOI: 10.1016/j.pt.2023.08.013 -
Nature Communications Jul 2023Malaria parasite lacks canonical pathways for amino acid biosynthesis and depends primarily on hemoglobin degradation and extracellular resources for amino acids....
Malaria parasite lacks canonical pathways for amino acid biosynthesis and depends primarily on hemoglobin degradation and extracellular resources for amino acids. Interestingly, a putative gene for glutamine synthetase (GS) is retained despite glutamine being an abundant amino acid in human and mosquito hosts. Here we show Plasmodium GS has evolved as a unique type I enzyme with distinct structural and regulatory properties to adapt to the asexual niche. Methionine sulfoximine (MSO) and phosphinothricin (PPT) inhibit parasite GS activity. GS is localized to the parasite cytosol and abundantly expressed in all the life cycle stages. Parasite GS displays species-specific requirement in Plasmodium falciparum (Pf) having asparagine-rich proteome. Targeting PfGS affects asparagine levels and inhibits protein synthesis through eIF2α phosphorylation leading to parasite death. Exposure of artemisinin-resistant Pf parasites to MSO and PPT inhibits the emergence of viable parasites upon artemisinin treatment.
Topics: Animals; Humans; Glutamate-Ammonia Ligase; Asparagine; Amino Acids; Glutamine; Plasmodium falciparum; Artemisinins; Parasites
PubMed: 37452051
DOI: 10.1038/s41467-023-39670-4 -
Philosophical Transactions of the Royal... Jan 2024The availability of high-quality data of helminth genomes provided over the past two decades has supported and accelerated large-scale 'omics studies and, consequently,... (Review)
Review
The availability of high-quality data of helminth genomes provided over the past two decades has supported and accelerated large-scale 'omics studies and, consequently, the achievement of a more in-depth molecular characterization of a number of pathogens. This has also involved spp. and since their genome was made available transcriptomics has been rather frequently applied to investigate gene expression regulation across their life cycle. proteomics characterization has instead been somehow neglected, with only a few reports performing high-throughput or targeted analyses associated with protein identification by tandem mass spectrometry. Such investigations are however necessary in order to discern important aspects associated with human strongyloidiasis, including understanding parasite biology and the mechanisms of host-parasite interaction, but also to identify novel diagnostic and therapeutic targets. In this review article, we will give an overview of the published proteomics studies investigating strongyloidiasis at different levels, spanning from the characterization of the somatic proteome and excretory/secretory products of different parasite stages to the investigation of potentially immunogenic proteins. Moreover, in the effort to try to start filling the current gap in host-proteomics, we will also present the first serum proteomics analysis in patients suffering from human strongyloidiasis. This article is part of the Theo Murphy meeting issue ': omics to worm-free populations'.
Topics: Animals; Humans; Strongyloides; Strongyloidiasis; Proteomics; Parasites; Host-Parasite Interactions
PubMed: 38008115
DOI: 10.1098/rstb.2022.0447 -
Parasite Immunology Dec 2023During inflammation, haematopoietic stem cells (HSCs) in the bone marrow (BM) and periphery rapidly expand and preferentially differentiate into myeloid cells that... (Review)
Review
During inflammation, haematopoietic stem cells (HSCs) in the bone marrow (BM) and periphery rapidly expand and preferentially differentiate into myeloid cells that mediate innate immune responses. HSCs can be directed into quiescence or differentiation by sensing alterations to the haematopoietic niche, including cytokines, chemokines, and pathogen-derived products. Most studies attempting to identify the mechanisms of haematopoiesis have focused on bacterial and viral infections. From intracellular protozoan infections to large multicellular worms, parasites are a global health burden and represent major immunological challenges that remain poorly defined in the context of haematopoiesis. Immune responses to parasites vary drastically, and parasites have developed sophisticated immunomodulatory mechanisms that allow development of chronic infections. Recent advances in imaging, genomic sequencing, and mouse models have shed new light on how parasites induce unique forms of emergency haematopoiesis. In addition, parasites can modify the haematopoiesis in the BM and periphery to improve their survival in the host. Parasites can also induce long-lasting modifications to HSCs, altering future immune responses to infection, inflammation or transplantation, a term sometimes referred to as central trained immunity. In this review, we highlight the current understanding of parasite-induced haematopoiesis and how parasites target this process to promote chronic infections.
Topics: Mice; Animals; Parasites; Persistent Infection; Hematopoiesis; Inflammation; Helminths
PubMed: 36797216
DOI: 10.1111/pim.12975 -
Parasitology Oct 2023Parasites and parasitologists have always lived together in good and bad luck in a sort of forced marriage. In recent times bad luck certainly prevailed, because of... (Review)
Review
Parasites and parasitologists have always lived together in good and bad luck in a sort of forced marriage. In recent times bad luck certainly prevailed, because of increasing man-made emergencies such as wars, chemical disasters, but also because of natural disasters, amplified by climate change, that condition more and more parasite–host equilibrium. The symposium at the National Congress of the Italian Society for Parasitology, was a first occasion for Italian parasitologists to reason about ‘disaster parasitology’ and researchers’ responsibilities. Extreme weather events and their impacts on parasites’ epidemiology are illustrated, comparing disasters that recently occurred in Italy with literature data. In particular, the Sardinian Island was hit subsequently by fires and floods exacerbating the effects on ecosystems and parasite–host-relationships. Examples of outbreaks in man and infections in various hosts after heavy rains are reviewed and effects of droughts on pasture borne parasites, such as gastro-intestinal nematodes of ruminants are discussed. Heavy rains may also cause dissemination of toxic substances released accidentally from chemical plants as happened e.g. in Milan province (IT) after the dioxin hazard. The overlapping effects of strictly man-made disasters with climate change dependent extreme weather events is further challenging the understanding of what are the consequences of disasters on ecosystems and parasite epidemiology.GIS applications combined with AI programs may help to face the complex challenges, allowing the collection and analysis of spatial/temporal data at whatever level desired. Examples illustrated in the article suggest their employment also in a more systematic, prevention-oriented manner.
Topics: Animals; Humans; Parasites; Weather; Ecosystem; Cryptosporidiosis; Cryptosporidium; Climate Change
PubMed: 37183698
DOI: 10.1017/S0031182023000471