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Suprabhat Mukherjee, Niladri Mukherjee, Prajna Gayen, Priya Roy, Santi P Sinha Babu
Human diseases caused by the infectious parasites have been one of the major problems throughout the evolutionary journey. Protozoan and metazoan parasitic infections result in a large number of deaths, disabilities and socio-economic loss worldwide to date. Despite our best efforts of developing suitable antiparasitics, these infections take a massive toll on human health. The prevalence of emerging resistance to the existing drugs, lack of efficacy and toxic side effects came out as added complications. Being enlisted under 'neglected' category, serious diseases like leishmaniases, filariases, trypanosomiases etc...
October 4, 2016: Current Drug Metabolism
Gagandeep S Saggu, Zarna R Pala, Shilpi Garg, Vishal Saxena
The MEP (Methyl Erythritol Phosphate) isoprenoids biosynthesis pathway is an attractive drug target to combat malaria, due to its uniqueness and indispensability for the parasite. It is functional in the apicoplast of Plasmodium and its products get transported to the cytoplasm, where they participate in glycoprotein synthesis, electron transport chain, tRNA modification and several other biological processes. Several compounds have been tested against the enzymes involved in this pathway and amongst them Fosmidomycin, targeted against IspC (DXP reductoisomerase) enzyme and MMV008138 targeted against IspD enzyme have shown good anti-malarial activity in parasite cultures...
2016: Frontiers in Microbiology
Jane H Kinnaird, Meetali Singh, Victoria Gillan, William Weir, Ewen Dd Calder, Isabel Hostettler, Utpal Tatu, Eileen Devaney, Brian R Shiels
HSP90 chaperones are essential regulators of cellular function, as they ensure the appropriate conformation of multiple key client proteins. Four HSP90 isoforms were identified in the protozoan parasite Theileria annulata. Partial characterisation was undertaken for three and localisation confirmed for cytoplasmic (TA12105); endoplasmic reticulum (TA06470) and apicoplast (TA10720) forms. ATPase activity and binding to the HSP90 inhibitor geldanamycin, were demonstrated for recombinant TA12105 and all three native forms could be isolated to varying extents by binding to geldanamycin beads...
September 20, 2016: Cellular Microbiology
Maude F Lévêque, Hoa Mai Nguyen, Sébastien Besteiro
Toxoplasma gondii and other apicomplexan parasites contain a peculiar non-photosynthetic plastid called the apicoplast, which is essential for their survival. The localization of autophagy-related protein ATG8 to the apicoplast in several apicomplexan species and life stages has recently been described, and we have shown this protein is essential for proper inheritance of this complex plastid into daughter cells during cell division. Although the mechanism behind ATG8 association to the apicoplast in T. gondii is related to the canonical conjugation system leading to autophagosome formation, its singular role seems independent from the initial catabolic purpose of autophagy...
July 2016: Communicative & Integrative Biology
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0159603.].
2016: PloS One
Saman Habib, Suniti Vaishya, Kirti Gupta
The protein translation machineries of the apicoplast and mitochondrion-the two actively translating organelles of apicomplexan parasites-have potential sites for drug intervention against diseases caused by these organisms. Work in the past few years, particularly on Plasmodium falciparum and Toxoplasma gondii, has shown that a reduced machinery of enzymes and factors is sufficient for organellar translation, which is also supported by components shared with the cytosolic translation system. This interplay between eukaryotic and prokaryotic-like components for mRNA translation in organelles is reviewed here...
August 12, 2016: Trends in Parasitology
Souad Amiar, James I MacRae, Damien L Callahan, David Dubois, Giel G van Dooren, Melanie J Shears, Marie-France Cesbron-Delauw, Eric Maréchal, Malcolm J McConville, Geoffrey I McFadden, Yoshiki Yamaryo-Botté, Cyrille Y Botté
Most apicomplexan parasites possess a non-photosynthetic plastid (the apicoplast), which harbors enzymes for a number of metabolic pathways, including a prokaryotic type II fatty acid synthesis (FASII) pathway. In Toxoplasma gondii, the causative agent of toxoplasmosis, the FASII pathway is essential for parasite growth and infectivity. However, little is known about the fate of fatty acids synthesized by FASII. In this study, we have investigated the function of a plant-like glycerol 3-phosphate acyltransferase (TgATS1) that localizes to the T...
August 2016: PLoS Pathogens
Morgan E Milton, Jun-Yong Choe, Richard B Honzatko, Scott W Nelson
Plasmodium falciparum, the primary cause of malaria, contains a non-photosynthetic plastid called the apicoplast. The apicoplast exists in most members of the phylum Apicomplexa and has its own genome along with organelle-specific enzymes for its replication. The only DNA polymerase found in the apicoplast (apPOL) was putatively acquired through horizontal gene transfer from a bacteriophage and is classified as an atypical A-family polymerase. Here, we present its crystal structure at a resolution of 2.9Å...
October 9, 2016: Journal of Molecular Biology
R E R Nisbet, J L McKenzie
Many members of the Apicomplexa contain a remnant chloroplast, known as an apicoplast. The apicoplast encodes numerous genes, and loss of the organelle is lethal. Here, we present a summary of what is known about apicoplast transcription. Unlike plant chloroplasts, there is a single RNA polymerase, and initial transcription is polycistronic. RNA is then cleaved into tRNA, mRNA and rRNA molecules. Significant levels of antisense transcription have been reported, together with a single case of RNA editing. Polycistronic transcription is also observed in the related algae Chromera and Vitrella, which retain a photosynthetic chloroplast...
July 30, 2016: Molecular and Biochemical Parasitology
R Ellen R Nisbet, Davy P Kurniawan, Harrison D Bowers, Christopher J Howe
The apicoplast, an organelle found in Plasmodium and many other parasitic apicomplexan species, is a remnant chloroplast that is no longer able to carry out photosynthesis. Very little is known about primary transcripts and RNA processing in the Plasmodium apicoplast, although processing in chloroplasts of some related organisms (chromerids and dinoflagellate algae) shows a number of unusual features, including RNA editing and the addition of 3' poly(U) tails. Here, we show that many apicoplast transcripts are polycistronic and that there is extensive RNA processing, often involving the excision of tRNA molecules...
August 2016: Protist
Érica S Martins-Duarte, Maira Carias, Rossiane Vommaro, Namita Surolia, Wanderley de Souza
The apicomplexan protozoan Toxoplasma gondii, the causative agent of toxoplasmosis, harbors an apicoplast, a plastid-like organelle with essential metabolic functions. Although the FASII fatty acid biosynthesis pathway located in the apicoplast is essential for parasite survival, the cellular effects of FASII disruption in T. gondii had not been examined in detail. Here, we combined light and electron microscopy techniques - including focused ion beam scanning electron microscopy (FIB-SEM) - to characterize the effect of FASII disruption in T...
September 1, 2016: Journal of Cell Science
Liting Lim, Claire P Sayers, Christopher D Goodman, Geoffrey I McFadden
Apicoplasts are vestigial plastids in apicomplexan parasites like Plasmodium, the causative agent of malaria. Apicomplexan parasites are dependant on their apicoplasts for synthesis of various molecules that they are unable to scavenge in sufficient quantity from their host, which makes apicoplasts attractive drug targets. Proteins known as plastid phosphate translocators (pPTs) are embedded in the outer apicoplast membrane and are responsible for the import of carbon, energy and reducing power to drive anabolic synthesis in the organelle...
2016: PloS One
María Del Carmen Terrón, Fernando González-Camacho, Luis Miguel González, Daniel Luque, Estrella Montero
The invasive form of the apicomplexan parasite Babesia divergens, the free merozoite, invades the erythrocytes of host vertebrates, leading to significant pathology. Although invasion is an active process critical for parasite survival, it is not yet entirely understood. Using techniques to isolate the viable free merozoite, as well as electron microscopy, we undertook a detailed morphological study and explored the sub-cellular structure of the invasive B. divergens free merozoite after it had left the host cell...
July 5, 2016: Ticks and Tick-borne Diseases
Arnish Chakraborty
Malaria is a life-threatening tropical disease, caused by the intracellular parasite Plasmodium falciparum. The World Health Organization counts malaria as one of the top ten causes of worldwide death. The unavailability of a successful malaria vaccine and the ever-increasing instances of drug resistance in the malaria parasite demand the discovery of new targets within P. falciparum for the development of next generation antimalarials. Fortunately, all apicomplexan parasites, including P. falciparum harbor a relict, non-photosynthetic plastid known as the apicoplast...
August 1, 2016: Life Sciences
Christiane Voss, Karen Ehrenman, Godfree Mlambo, Satish Mishra, Kota Arun Kumar, John B Sacci, Photini Sinnis, Isabelle Coppens
UNLABELLED: Plasmodium parasites undergo continuous cellular renovation to adapt to various environments in the vertebrate host and insect vector. In hepatocytes, Plasmodium berghei discards unneeded organelles for replication, such as micronemes involved in invasion. Concomitantly, intrahepatic parasites expand organelles such as the apicoplast that produce essential metabolites. We previously showed that the ATG8 conjugation system is upregulated in P. berghei liver forms and that P...
2016: MBio
Xiao-Xuan Zhang, Wei Cong, Jian-Gang Ma, Zhi-Long Lou, Quan Zhao, Qing-Feng Meng, Ai-Dong Qian, Xing-Quan Zhu
Toxoplasma gondii can infect virtually all warm-blooded animals including foxes. However, little is known of the molecular epidemiology and genotypes of T. gondii infecting foxes in China. Therefore, the present study characterized T. gondii genotypes in foxes in China for the first time. During November 2014 to October 2015, brain tissue samples collected from 264 Arctic foxes (Vulpes lagopus) in Jilin, Heilongjiang and Shandong provinces were used to detect the T. gondii B1 gene by a semi-nested PCR, and the positive samples were genotyped at 10 nuclear loci (i...
October 2016: Infection, Genetics and Evolution
Morgan E Milton, Scott W Nelson
Members of the phylum Apicomplexa are responsible for many devastating diseases including malaria (Plasmodium spp.), toxoplasmosis (Toxoplasma gondii), babesiosis (Babesia bovis), and cyclosporiasis (Cyclospora cayetanensis). Most Apicomplexans contain a unique and essential organelle called the apicoplast. Derived from an ancient chloroplast, the apicoplast replicates and maintains a 35 kilobase (kb) circular genome. Due to its essential nature within the parasite, drugs targeted to proteins involved in DNA replication and repair of the apicoplast should be potent and specific...
August 2016: Molecular and Biochemical Parasitology
Melanie J Shears, James I MacRae, Vanessa Mollard, Christopher D Goodman, Angelika Sturm, Lindsey M Orchard, Manuel Llinás, Malcolm J McConville, Cyrille Y Botté, Geoffrey I McFadden
Malaria parasites can synthesize fatty acids via a type II fatty acid synthesis (FASII) pathway located in their apicoplast. The FASII pathway has been pursued as an anti-malarial drug target, but surprisingly little is known about its role in lipid metabolism. Here we characterize the apicoplast glycerol 3-phosphate acyltransferase that acts immediately downstream of FASII in human (Plasmodium falciparum) and rodent (P. berghei) malaria parasites and investigate how this enzyme contributes to incorporating FASII fatty acids into precursors for membrane lipid synthesis...
June 20, 2016: Cellular Microbiology
Avinaba Mukherjee, Gobinda Chandra Sadhukhan
OBJECTIVES: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the 'apicoplast', which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite...
March 2016: Journal of Pharmacopuncture
Charisse Flerida A Pasaje, Vanessa Cheung, Kit Kennedy, Erin E Lim, Jonathan B Baell, Michael D W Griffin, Stuart A Ralph
The malaria parasite Plasmodium falciparum relies on efficient protein translation. An essential component of translation is the tryptophanyl-tRNA synthetase (TrpRS) that charges tRNA(trp). Here we characterise two isoforms of TrpRS in Plasmodium; one eukaryotic type localises to the cytosol and a bacterial type localises to the remnant plastid (apicoplast). We show that the apicoplast TrpRS aminoacylates bacterial tRNA(trp) while the cytosolic TrpRS charges eukaryotic tRNA(trp). An inhibitor of bacterial TrpRSs, indolmycin, specifically inhibits aminoacylation by the apicoplast TrpRS in vitro, and inhibits ex vivo Plasmodium parasite growth, killing parasites with a delayed death effect characteristic of apicoplast inhibitors...
2016: Scientific Reports
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