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An Introduction to Parasitism
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Also to be mentioned here is Cryptosporidum, a water-borne parasite genus with many species that are frequently implicated in outbreaks of diarrhea. Cryptosporidium has been considered an intracellular parasite, but new revelations (see Chapter 2 also) have suggested it might best be considered an epicellular parasite. As shown in Figure 1.7, the parasite induces a host gut cell to assist in forming a membrane called a parasitophorous vacuole around itself that separates it from the host cytoplasm. In this epicellular location, it draws nutrients from the host cell through a feeding tube by a process called myzocytosis. If nutrient conditions are right, the parasite can even develop without feeding on a host cell.
Cryptosporidium spp
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
As discussed earlier (Section II.B), Cryptosporidium spp. reside within a parasitophorous vacuole that is confined to the microvillous region of enterocytes. Parasites grown in chicken embryos and in cultured cells also assume a similar intracellular, extracytoplasmic position. Thus, regardless of host-cell type, developmental stages of Cryptosporidium spp. are confined to a parasitophorous vacuole that bulges outward beneath the host-cell surface and that is apparently prevented from migrating into the perinuclear region by a dense network of filaments that form beneath its base in the host-cell cytoplasm. The portion of the parasite separated from the host-cell cytoplasm by the microfilamentous sheet undergoes extensive membrane folding to form what has been called the feeder organelle. To date, I am not aware of any physiological evidence of nutrient transport into the parasite through this unique species-tospecies interface.
The malaria parasites
Published in David A Warrell, Herbert M Gilles, Essential Malariology, 2017
Robert E Sinden, Herbert M Gilles
Within the parasitophorous vacuole, the merozoite releases the contents of the microspheres through the parasite surface. The contents of these spheres induce proliferation of the parasitophorous vacuole membrane (PVM). It is assumed this expansion allows the more rapid exchange of small molecules between red blood cell cytoplasm and the parasite. The changes induced in the red blood cell by the growing trophozoites become more pronounced as the parasite develops. The species-specific nature of the changes has long been recognized, e.g. Maurer’s clefts, Schüffher’s dots etc., and is useful in species identification (Figure 2.9). The PVM is clearly a composite structure, derived from both red blood cell and parasite components in that it initially has a markedly reduced number of intramembranous particles (IMPs) compared to either the red blood cell or merozoite plasma membrane.
Drug-like molecules with anti-trypanothione synthetase activity identified by high throughput screening
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Diego Benítez, Jaime Franco, Florencia Sardi, Alejandro Leyva, Rosario Durán, Gahee Choi, Gyongseon Yang, Taehee Kim, Namyoul Kim, Jinyeong Heo, Kideok Kim, Honggun Lee, Inhee Choi, Constantin Radu, David Shum, Joo Hwan No, Marcelo A. Comini
Our biological data also show an overall higher selectivity index towards T. brucei for the hits from the in-house library than for those from the ENAMINE library, and highlights the difficulties in identifying bioactive and selective compounds acting on the intracellular form of pathogenic trypanosomatids (e.g. T. cruzi and L. infantum). Differences in the proteome of the infective stage of trypanosomatid species and/or in the molecular targets of the hits may in part account for the low attrition rate. On the other hand, compound metabolisation, sequestration, efflux or modification by the host cell are additional factors that may affect the bioactivity against intracellular pathogens and represent major challenges for drug development. Worth noting, at least three hits (4, 5 and 7) showed a killing potency against T. cruzi amastigotes in the same order of magnitude than that of the clinical drug benznidazole. Although several hits from the in-house library were active against L. donovani amastigotes, selectivity was highly compromised. Leishmania amastigotes reside in the parasitophorous vacuole of macrophages, a hybrid compartment derived from the host endocytic- and containing elements from the secretory-pathway67. In addition, to its extreme low pH (4.7–5.3)68, the parasitophorous vacuole contains several hydrolytic, proteolytic and efflux activities that may eventually reduce compounds bioavailability and activity. Importantly, our study identified seven new biological hits against bloodstream T. brucei.
Current pharmacotherapy of cryptosporidiosis: an update of the state-of-the-art
Published in Expert Opinion on Pharmacotherapy, 2021
Anne Schneider, Sebastian Wendt, Christoph Lübbert, Henning Trawinski
Considerable research has examined the development of novel treatment options over the past years, but cryptosporidiosis pharmacotherapy remains challenging. As Cryptosporidium spp. parasitizes intracellularly, it is harder for anti-infective agents to reach [2]. Current models show that the parasite is separated from the host epithelial cell cytosol by an electron-dense band, but embraced by a host cell-derived parasitophorous vacuole membrane facing the intestinal lumen [30]. Systemic drugs need to cross through the selective electron-dense band and feeder organelle, while luminal non-systemic drugs may directly act on the parasite through the parasitophorous vacuole membrane [30]. Furthermore, while chronic cryptosporidiosis effects – such as damage of the intestinal barrier and glucose malabsorption – are known, underlying pathogenetic mechanisms are not well understood [31].
Prospects for antimicrobial peptide-based immunotherapy approaches in Leishmania control
Published in Expert Review of Anti-infective Therapy, 2018
Farnaz Zahedifard, Sima Rafati
The discovery of Penicillin in 1928 changed human life forever [57]. Microbial territories were conquered by sequential generations of antibiotics, although new obstacles such as drug resistance were encountered afterwards. In general, designing drugs against bacterial pathogens is easier in comparison with intracellular parasites. This is mainly due to the differences between eukaryotic and prokaryotic cell structure, which provides the opportunity to find molecules that are safer for human use and target the bacteria specifically. However, with similarity between parasites such as unicellular eukaryotes and human cells, there are more challenges in producing suitable safe drugs. In addition, the drug candidate should be able to pass through the host cell membrane safely and reach the parasitophorous vacuole where amastigote forms multiply in a well-established shelter.