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Microbiology and Molecular Biology... Jun 2022Parasites belonging to the Apicomplexa phylum are among the most successful pathogens known in nature. They can infect a wide range of hosts, often remain undetected by... (Review)
Review
Parasites belonging to the Apicomplexa phylum are among the most successful pathogens known in nature. They can infect a wide range of hosts, often remain undetected by the immune system, and cause acute and chronic illness. In this phylum, we can find parasites of human and veterinary health relevance, such as , , , and . There are still many unknowns about the biology of these pathogens due to the ethical and practical issues of performing research in their natural hosts. Animal models are often difficult or nonexistent, and as a result, there are apicomplexan life cycle stages that have not been studied. One recent alternative has been the use of three-dimensional (3D) systems such as organoids, 3D scaffolds with different matrices, microfluidic devices, organs-on-a-chip, and other tissue culture models. These 3D systems have facilitated and expanded the research of apicomplexans, allowing us to explore life stages that were previously out of reach and experimental procedures that were practically impossible to perform in animal models. Human- and animal-derived 3D systems can be obtained from different organs, allowing us to model host-pathogen interactions for diagnostic methods and vaccine development, drug testing, exploratory biology, and other applications. In this review, we summarize the most recent advances in the use of 3D systems applied to apicomplexans. We show the wide array of strategies that have been successfully used so far and apply them to explore other organisms that have been less studied.
Topics: Animals; Apicomplexa; Cryptosporidiosis; Cryptosporidium; Parasites; Plasmodium; Toxoplasma
PubMed: 35412359
DOI: 10.1128/mmbr.00025-22 -
Briefings in Functional Genomics Sep 2019Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained... (Review)
Review
Two simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained recognition among scientists and public health officials. Notwithstanding, these species and others including Plasmodium coatneyi have served for decades as sources of knowledge on the biology, genetics and evolution of Plasmodium, and the diverse ramifications and outcomes of malaria in their monkey hosts. Experimental analysis of these species can help to fill gaps in knowledge beyond what may be possible studying the human malaria parasites or rodent parasite species. The genome sequences for these simian malaria parasite species were reported during the last decade, and functional genomics research has since been pursued. Here research on the functional genomics analysis involving these species is summarized and their importance is stressed, particularly for understanding host-parasite interactions, and potentially testing novel interventions. Importantly, while Plasmodium falciparum and Plasmodium vivax can be studied in small New World monkeys, the simian malaria parasites can be studied more effectively in the larger Old World monkey macaque hosts, which are more closely related to humans. In addition to ex vivo analyses, experimental scenarios can include passage through Anopheline mosquito hosts and longitudinal infections in monkeys to study acute and chronic infections, as well as relapses, all in the context of the in vivo host environment. Such experiments provide opportunities for understanding functional genomic elements that govern host-parasite interactions, immunity and pathogenesis in-depth, addressing hypotheses not possible from in vitro cultures or cross-sectional clinical studies with humans.
Topics: Animals; Genomics; Host-Parasite Interactions; Humans; Plasmodium; Plasmodium cynomolgi; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium vivax; Primates; Systems Biology
PubMed: 31241151
DOI: 10.1093/bfgp/elz013 -
International Journal For Parasitology.... Dec 2020Cryptosporidium and Toxoplasma are parasites that have caused problems worldwide. Cryptosporidium causes severe watery diarrhoea and may be fatal in immunocompromised...
Cryptosporidium and Toxoplasma are parasites that have caused problems worldwide. Cryptosporidium causes severe watery diarrhoea and may be fatal in immunocompromised patients and in infants. Nitazoxanide is the only agent currently approved by the FDA, but its efficacy is limited. Toxoplasmosis is also a problem in the immunocompromised, as currently available treatment options have limited efficacy and patient tolerance can be poor. In the present investigation, we screened libraries of epigenetic compounds to identify those that inhibited C. parvum growth. Nullscript was identified as a compound with an inhibitory effect on C. parvum and T. gondii growth, and was less toxic to host cells. Nullscript was also able to significantly decrease oocyst excretion in C. parvum-infected SCID mice.
Topics: Animals; Cryptosporidiosis; Cryptosporidium; Cryptosporidium parvum; Humans; Mice; Mice, SCID; Toxoplasma
PubMed: 33120250
DOI: 10.1016/j.ijpddr.2020.10.004 -
Current Biology : CB Sep 2019The apicomplexans are a group of obligate animal pathogens that include Plasmodium (malaria), Toxoplasma (toxoplasmosis), and Cryptosporidium (cryptosporidiosis) [1]....
The apicomplexans are a group of obligate animal pathogens that include Plasmodium (malaria), Toxoplasma (toxoplasmosis), and Cryptosporidium (cryptosporidiosis) [1]. They are an extremely diverse and specious group but are nevertheless united by a distinctive suite of cytoskeletal and secretory structures related to infection, called the apical complex, which is used to recognize and gain entry into animal host cells. The apicomplexans are also known to have evolved from free-living photosynthetic ancestors and retain a relict plastid (the apicoplast), which is non-photosynthetic but houses a number of other essential metabolic pathways [2]. Their closest relatives include a mix of both photosynthetic algae (chromerids) and non-photosynthetic microbial predators (colpodellids) [3]. Genomic analyses of these free-living relatives have revealed a great deal about how the alga-parasite transition may have taken place, as well as origins of parasitism more generally [4]. Here, we show that, despite the surprisingly complex origin of apicomplexans from algae, this transition actually occurred at least three times independently. Using single-cell genomics and transcriptomics from diverse uncultivated parasites, we find that two genera previously classified within the Apicomplexa, Piridium and Platyproteum, form separately branching lineages in phylogenomic analyses. Both retain cryptic plastids with genomic and metabolic features convergent with apicomplexans. These findings suggest a predilection in this lineage for both the convergent loss of photosynthesis and transition to parasitism, resulting in multiple lineages of superficially similar animal parasites.
Topics: Animals; Apicomplexa; Apicoplasts; Biological Evolution; Parasites; Phylogeny
PubMed: 31422883
DOI: 10.1016/j.cub.2019.07.019 -
Experimental Parasitology Sep 2017Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of... (Review)
Review
Many life-cycle processes in parasites are regulated by protein phosphorylation. Hence, disruption of essential protein kinase function has been explored for therapy of parasitic diseases. However, the difficulty of inhibiting parasite protein kinases to the exclusion of host orthologues poses a practical challenge. A possible path around this difficulty is the use of bumped kinase inhibitors for targeting calcium-dependent protein kinases that contain atypically small gatekeeper residues and are crucial for pathogenic apicomplexan parasites' survival and proliferation. In this article, we review efficacy against the kinase target, parasite growth in vitro, and in animal infection models, as well as the relevant pharmacokinetic and safety parameters of bumped kinase inhibitors.
Topics: Animals; Antiprotozoal Agents; Apicomplexa; Benzimidazoles; Humans; Imidazoles; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Protozoan Infections; Pyridines
PubMed: 28065755
DOI: 10.1016/j.exppara.2017.01.001 -
Current Opinion in Microbiology Dec 2022Members of the Apicomplexa phylum are unified by an apical complex tailored for motility and host cell invasion. It includes regulated secretory organelles and a conoid... (Review)
Review
Members of the Apicomplexa phylum are unified by an apical complex tailored for motility and host cell invasion. It includes regulated secretory organelles and a conoid attached to the apical polar ring (APR) from which subpellicular microtubules emerge. In coccidia, the conoid is composed of a cone of spiraling tubulin fibers, two preconoidal rings, and two intraconoidal microtubules. The conoid extrudes through the APR in motile parasites. Recent advances in proteomics, cryo-electron tomography, super-resolution, and expansion microscopy provide a more comprehensive view of the spatial and temporal resolution of proteins belonging to the conoid subcomponents. In combination with the phenotyping of targeted mutants, the biogenesis, turnover, dynamics, and function of the conoid begin to be elucidated.
Topics: Toxoplasma; Apicomplexa; Cytoskeleton; Microtubules; Organelles
PubMed: 36332501
DOI: 10.1016/j.mib.2022.102226 -
Cellular Microbiology Jul 2020The ability of eukaryotic parasites from the phylum Apicomplexa to cause devastating diseases is predicated upon their ability to maintain faithful and precise protein... (Review)
Review
The ability of eukaryotic parasites from the phylum Apicomplexa to cause devastating diseases is predicated upon their ability to maintain faithful and precise protein trafficking mechanisms. Their parasitic life cycle depends on the trafficking of effector proteins to the infected host cell, transport of proteins to several critical organelles required for survival, as well as transport of parasite and host proteins to the digestive organelles to generate the building blocks for parasite growth. Several recent studies have shed light on the molecular mechanisms parasites utilise to transform the infected host cells, transport proteins to essential metabolic organelles and for biogenesis of organelles required for continuation of their life cycle. Here, we review key pathways of protein transport originating and branching from the endoplasmic reticulum, focusing on the essential roles of chaperones in these processes. Further, we highlight key gaps in our knowledge that prevents us from building a holistic view of protein trafficking in these deadly human pathogens.
Topics: Animals; Apicomplexa; Apicoplasts; Endoplasmic Reticulum; Humans; Malaria; Parasites; Protein Transport; Protozoan Proteins; Vacuoles
PubMed: 32388921
DOI: 10.1111/cmi.13215 -
Experimental Parasitology Jan 2019Cryptosporidium is a genus of single celled parasites capable of infecting a wide range of animals including humans. Cryptosporidium species are members of the phylum... (Review)
Review
Cryptosporidium is a genus of single celled parasites capable of infecting a wide range of animals including humans. Cryptosporidium species are members of the phylum apicomplexa, which includes well-known genera such as Plasmodium and Toxoplasma. Cryptosporidium parasites cause a severe gastro-intestinal disease known as cryptosporidiosis. They are one of the most common causes of childhood diarrhoea worldwide, and infection can have prolonged detrimental effects on the development of children, but also can be life threatening to HIV/AIDS patients and transplant recipients. A variety of hosts can act as reservoirs, and Cryptosporidium can persist in the environment for prolonged times as oocysts. While there has been substantial interest in these parasites, there is very little progress in terms of treatment development and understanding the majority of the life cycle of this unusual organism. In this review, we will provide an overview on the existing knowledge of the biology of the parasite and the current progress in developing in vitro cultivation systems. We will then describe a synopsis of current and next generation approaches that could spearhead further research in combating the parasite.
Topics: Animals; Cell Line; Cryptosporidiosis; Cryptosporidium; Humans; Life Cycle Stages; Phylogeny; Research; Research Design
PubMed: 30521793
DOI: 10.1016/j.exppara.2018.12.001 -
Parasites & Vectors May 2019The epidemiology of feline vector-borne pathogens (FeVBPs) has been less investigated in cats than in dogs. The present study assessed the prevalence of Rickettsia spp.,...
BACKGROUND
The epidemiology of feline vector-borne pathogens (FeVBPs) has been less investigated in cats than in dogs. The present study assessed the prevalence of Rickettsia spp., Babesia spp., Cytauxzoon spp. and Leishmania infantum infections in cat populations living in central Italy, by molecular and serological tools.
RESULTS
A total of 286 healthy cats were randomly selected from catteries and colonies in central Italy. Peripheral blood and conjunctival swab (CS) samples were collected during surgical procedures for regional neutering projects. Sera were analysed by IFAT to detect anti-Rickettsia felis, R. conorii, Babesia microti and Leishmania IgG antibodies using commercial and home-made antigens. DNA extracted from buffy coats (BCs) was tested for Rickettsia spp., and Piroplasmida species, including Cytauxzoon spp. and Babesia spp. by PCR. Buffy coats and CS samples were assayed by a nested (n)-PCR for Leishmania spp. Sixty-two cats (21.67%) were seropositive to at least one of the tested pathogens. The serological assay revealed 23 (8.04%) and 18 (6.29%) positive cats for R. felis and R. conorii, respectively, with low titers (1/64-1/128). No antibodies against B. microti were detected. Neither Rickettsia nor Piroplasmida DNA were amplified using the specific PCR assays. Thirty-one cats (10.83%) tested positive to anti-Leishmania IgG, with titers ranging from 1:40 to 1:160 and 45 animals (15.73%) tested positive to Leishmania CS n-PCR, whereas none of the animals tested positive to BC n-PCR. Considering the results obtained by IFAT and CS n-PCR, a moderate agreement between the two tests was detected (κ = 0.27).
CONCLUSIONS
The results of the serological and molecular surveys showed a moderate exposure to Leishmania in the investigated cats and highlighted the limited molecular diagnostic value of BC versus CS samples for this pathogen. Conversely no evidence supported the circulation of Cytauxzoon spp. in domestic cats, in contrast with previous detections in European wild cats in the same areas monitored. The low positive titres for R. felis in association with no DNA BC amplification prevent speculation on the exposure of feline populations to this FeVBP due to the cross-reactivity existing within spotted fever group rickettsiosis (SFGR).
Topics: Animals; Apicomplexa; Babesia; Cat Diseases; Cats; Communicable Diseases, Emerging; Cross-Sectional Studies; Female; Italy; Leishmania infantum; Male; Protozoan Infections, Animal; Rickettsia; Rickettsia Infections
PubMed: 31046822
DOI: 10.1186/s13071-019-3409-8 -
Fungal Biology May 2021TPPP-like proteins, exhibiting microtubule stabilizing function, constitute a eukaryotic superfamily, characterized by the presence of the p25alpha domain. TPPPs in the...
TPPP-like proteins, exhibiting microtubule stabilizing function, constitute a eukaryotic superfamily, characterized by the presence of the p25alpha domain. TPPPs in the strict sense are present in animals except Trichoplax adhaerens, which instead contains apicortin where a part of the p25alpha domain is combined with a DCX domain. Apicortin is absent in other animals and occurs mostly in the protozoan phylum, Apicomplexa. A strong correlation between the occurrence of p25alpha domain and that of the eukaryotic cilium/flagellum was suggested. Species of the deeper branching clades of Fungi possess flagellum but others lost it thus investigation of fungal genomes can help testing of this suggestion. Indeed, these proteins are present in early branching Fungi. Both TPPP and apicortin are present in Rozellomycota (Cryptomycota) and Chytridiomycota, TPPP in Blastocladiomycota, apicortin in Neocallimastigomycota, Monoblepharomycota and the non-flagellated Mucoromycota. Beside the "normal" TPPP occurring in animals, a special, fungal-type TPPP is also present in Fungi, in which a part of the p25alpha domain is duplicated. Dikarya, the most developed subkingdom of Fungi, lacks both flagellum and TPPPs. Thus it is strengthened that each ciliated/flagellated organism contains p25alpha domain-containing proteins while there are very few non-flagellated ones where p25alpha domain can be found.
Topics: Animals; Apicomplexa; Fungal Proteins; Fungi
PubMed: 33910677
DOI: 10.1016/j.funbio.2020.12.001