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An Overview of Parasite Diversity
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Among the most prominent of all parasites, also falling into the Discoba lineage, are the kinetoplastids, represented by Trypanosoma (see Figure 2.9C) and Leishmania. Representatives of the former genus cause sleeping sickness and Chagas disease whereas Leishmania species cause a variety of forms of leishmaniasis. These parasites are discussed extensively throughout the book. Others, like Phytomonas, are important parasites of plants like coffee and palm trees. Kinetoplastids are unusual in possessing a single mitochondrion that contains a kinetoplast. The kinetoplast contains a network of concatenated circular DNA molecules (assembled like the chain mail in armor), some of which are maxicircles that encode in a peculiar, encrypted fashion the usual mitochondrial gene products. Many minicircles are also present and encode guide RNAs, which are used to decode the encrypted maxicircles. Guide RNAs either insert or delete uridine residues in maxicircle transcripts to accomplish this. It is not clear why kinetoplastids use this unusual RNA editing process. It may have been derived from genes transferred horizontally from viruses. Whatever the origin or purpose, it is clear that disabling RNA editing is lethal for kinetoplastids. Kinetoplastids are also unusual for sequestering the enzymes of glycolysis within distinct, membrane-bound glycosomes.
Host Defenses Against Prototypical Intracellular Protozoans, the Leishmania
Published in Peter D. Walzer, Robert M. Genta, Parasitic Infections in the Compromised Host, 2020
Richard D. Pearson, Mary E. Wilson
Leishmania species exist in two basic morphological forms during their life cycle (3). In humans and animats, they are found within mononuclear phagocytes as oval intracellular amastigotes that are 2-3 /μm in length and lack an exteriorized flagellum (Fig. 1). In Giemsa or Wright-Giemsa stained preparations, the nucleus appears relatively large and red. The kinetoplast, a specialized mitochondrial structure that contains extranuclear DNA, stains intensely red and appears as a distinctive rod-shaped body. Leishmania multiply by fission (Fig. 2). The amastigote converts to and multiplies as a flagellated, extracellular promastigote in the gut of its arthropod vector, the sandfly (Figs. 3 and 4). Promastigotes are pleomorphic and vary in size as they mature. They have pear- or spindle-shaped bodies approximately 10-15 μm in length and 1.5-3.5 μm in width, with a flagellum that is 15-28 μm long. A number of culture media support the growth of promastigotes in vitro (7).
Trypanosoma cruzi
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Paula Andrea Jiménez, Jesus Eduardo Jaimes, Juan David Ramírez
Members of the order Kinetoplastida are unicellular organisms characterized by the presence of flagellum and a prominent and paraflagellar structure known as kinetoplast corresponding to mitochondrial DNA condensation located inside a single mitochondrion that is branched throughout the cell [8]. The life stages of the parasite demonstrate diversity in their morphology, location of the kinetoplast, mobility, and reproductive capacity. The following cellular stages of the parasite are observed: Amastigote: The oval-shaped, replicative form that is present at the intracellular level in the vertebrate hosts and lacks mobility. The kinetoplast is located posterior to the nucleus.Epimastigote: The elongated, replicative form that contains the flagellum and a short undulating membrane with limited mobility. The kinetoplast is located posterior to the nucleus. Replication is by binary fission in the anterior portion of the digestive system of the vector. It is also the form developed in axenic cultures.Trypomastigote: The elongated form that lacks replicative activity, has a flagellum and a prominent undulating membrane so it is highly mobile. The kinetoplast is located in the anterior part of the nucleus. The metacyclic form is found in the rectal ampulla of the vector and the circulating form in the vertebrate host.
Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents
Published in Expert Opinion on Therapeutic Patents, 2023
Francesco Melfi, Simone Carradori, Cristina Campestre, Entela Haloci, Alessandra Ammazzalorso, Rossella Grande, Ilaria D’Agostino
Pentamidine (Figure 1) is an aromatic diamidine used since the 1930s. The rationale for using diamidines was based on their hypoglycemic effect and the intent to starve the trypanosomes of their source of nutrients. Moreover, the diamidines are known to act with a trypanocidal effect, whose mechanism of action has been widely studied, and several proposals were made. It seems that pentamidine can bind to T. brucei DNA double helix at adenine-thymine-rich regions in the minor groove, forming cross-linkages between two adenines, preferentially four to five base pairs apart. Moreover, pentamidine is a reversible inhibitor of trypanosomal S-adenosylmethionine decarboxylase (SAMDC), impairing the mechanism of polyamines synthesis [4]. Likewise, other modes of action are kinetoplast fragmentation and inhibition of the biosynthetic pathways for proteins and phospholipids [5].
Drugs and nanoformulations for the management of Leishmania infection: a patent and literature review (2015-2022)
Published in Expert Opinion on Therapeutic Patents, 2023
Mariana Verdan, Igor Taveira, Flávia Lima, Fernanda Abreu, Dirlei Nico
According to advances in the complete genome sequencing of Leishmania species searching for new molecular targets in the parasite is a hot point in developing new anti-Leishmania drugs. Enzymes are attractive molecular targets since they participate in metabolic pathways essential to the parasite’s survival and thus ensure its survival in the vertebrate host. Therefore, DNA topoisomerases from Leishmania assume an essential study target for designing new drugs capable of causing enzymatic inhibition [70]. Topoisomerases are involved in fundamental stages of the parasite’s life cycle and in the parasite DNA replication and transcription processes [71]. Parasites of the genus Leishmania have a specific structure called kinetoplast formed by circular DNA called kDNA, whose duplication undergoes the action of specific topoisomerases, making these excellent molecular targets [72].
Why hasn’t there been more progress in new Chagas disease drug discovery?
Published in Expert Opinion on Drug Discovery, 2020
Alane Beatriz Vermelho, Giseli Capaci Rodrigues, Claudiu T. Supuran
Another strategy is to identify the pathogen genome by PCR [6]. In the 1980’s, the introduction of the recently developed polymerase chain reaction (PCR) assay, in particular, held promises of high sensitivity, specificity, and high-throughput potential. First PCR were done with the major molecular component of the mitochondrial DNA (kinetoplast). In 2014, short and stable RNA aptamers were introduced to facilitate the PCR-based detection method. The PCR-based technique also has limitations and is significantly affected by the fluctuations in parasitemia that characterize the chronic phase of Chagas disease, and by inter-DTU variations in dosage and/or sequence of the targets of amplification. In addition, PCR detection of trypomastigotes in blood is sometimes difficult due to their low concentration and the small section of tissue or volume of blood tested by PCR; thus increasing the risk of false negative outcomes [6,49].