Active invasion and/or encapsulation? A reappraisal of host-cell parasitism by Cryptosporidium

Borowski, Hanna; Clode, Peta L.; Thompson, R.C.A.

doi:10.1016/j.pt.2008.08.002

Cited by 59 publications

(59 citation statements)

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“…To place TgAMA4 and TgRON2 L1 in the broader context of AMA and RON2 family members, we first performed a phylogenetic analysis. Custom homology searches of TgAMA1 and TgRON2 against predicted protein sets of apicomplexans from EuPathDB (eupathdb.org/eupathdb/) recovered sequences of AMA and RON2-like proteins from diverse lineages, except Cryptosporidium, consistent with the lack of a moving junction-dependent invasion mechanism in this atypical apicomplexan (21). Phylogenetic analysis of AMA-like proteins recovered two deeply branching clades.…”

Section: Resultsmentioning

confidence: 74%

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA–RON2 pair

Parker

Penarete-Vargas

Hamilton

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the host cell, where parasite-derived rhoptry neck protein 2 (RON2) family members localize to the host outer membrane and serve as ligands for apical membrane antigen (AMA) family surface proteins displayed on the parasite. Recently, we showed that T. gondii harbors a novel AMA designated as TgAMA4 that shows extreme sequence divergence from all characterized AMA family members. Here we show that sporozoite-expressed TgAMA4 clusters in a distinct phylogenetic clade with Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) proteins and forms a high-affinity, functional complex with its coevolved partner, TgRON2 L1 . High-resolution crystal structures of TgAMA4 in the apo and TgRON2 L1 -bound forms complemented with alanine scanning mutagenesis data reveal an unexpected architecture and assembly mechanism relative to previously characterized AMA-RON2 complexes. Principally, TgAMA4 lacks both a deep surface groove and a key surface loop that have been established to govern RON2 ligand binding selectivity in other AMAs. Our study reveals a previously underappreciated level of molecular diversity at the parasite-host-cell interface and offers intriguing insight into the adaptation strategies underlying sporozoite invasion. Moreover, our data offer the potential for improved design of neutralizing therapeutics targeting a broad range of AMA-RON2 pairs and apicomplexan invasive stages.Apicomplexa | Toxoplasma gondii | invasion | moving junction | X-ray crystallography P hylum Apicomplexa comprises >5,000 parasitic protozoan species, many of which cause devastating diseases on a global scale. Two of the most prevalent species are Toxoplasma gondii and Plasmodium falciparum, the causative agents of toxoplasmosis and severe human malaria, respectively (1, 2). The obligate intracellular apicomplexan parasites lead complex and diverse lifestyles that require invasion of many different cell types. Despite this diversity of target host cells, most apicomplexans maintain a generally conserved mechanism for active invasion (3). The parasite initially glides over the surface of a host cell and then reorients to place its apical end in close contact to the hostcell membrane. After this initial attachment, a circumferential ring of adhesion (termed the moving or tight junction) is formed, through which the parasite actively propels itself while concurrently depressing the host-cell membrane to create a nascent protective vacuole (4).Formation of the moving junction relies on a pair of highly conserved parasite proteins: rhoptry neck protein 2 (RON2) and apical membrane antigen 1 (AMA1). Initially, parasites discharge RON2 into the host cell membrane where an extracellular portion (domain 3; D3) serves as a ligand for AMA1 displa...

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Section: Resultsmentioning

confidence: 74%

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA–RON2 pair

Parker

Penarete-Vargas

Hamilton

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Furthermore, studies in vitro combined with observations in mice (Hijjawi et al 2001(Hijjawi et al , 2002(Hijjawi et al , 2004 revealed that the development of Cryptosporidium comprises an extracellular phase, thus showing that Cryptosporidium is not an obligatory intracellular pathogen as previously thought. These studies also emphasized the superficial, epicellular nature of the relationship the parasite has with its host cell (Barta and Thompson, 2006 ;Butaeva et al 2006 ;Borowski et al 2008 ;Valigurova et al 2008).…”

Section: Cryptosporidiummentioning

confidence: 99%

“…This suggests that the feeding organelle that is seen in Cryptosporidium species may represent an evolutionary modification to the ancestral myzocytotic morphological adaptations (Barta and Thompson, 2006). Apart from size, the only difference between the two modes of feeding is that Cryptosporidium has evolved a way to induce the host cell to overlay it with an extension of the host cell membrane (Barta and Thompson, 2006 ;Borowski et al 2008). Physical ingestion of host cell cytoplasm has not been observed in Cryptosporidium as it has for dinoflagellates, perkinsids, colpodellids and some gregarines.…”

Section: Cryptosporidiummentioning

confidence: 99%

“…We also know very little about the pathogenesis of cryptosporidial infections and the relative contribution of ' intracellular ' and extracellular phases of development to disease processes and epidemiology (Borowski et al 2008). In this respect, and as pointed out by Dionisio (2002), it is interesting that no correlation has been found between histological intensity of Cryptosporidium infections and clinical severity (Manabe et al 1998).…”

Section: Cryptosporidiummentioning

confidence: 99%

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Echinococcus,GiardiaandCryptosporidium: observational studies challenging accepted dogma

Thompson

2009

Parasitology

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in vitro culture systems that allow the maintenance, and support the development of Echinococcus, Giardia and Cryptosporidium in the laboratory have had a significant impact on their biology and taxonomy and the epidemiology of infections they cause. This short retrospective review demonstrates how radical shifts in our understanding have occurred as a result of being able to grow these organisms in culture, and how molecular tools have helped in the interpretation of such research that often reflects the observations of earlier workers.

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“…São monoxênicos e se distinguem de outros coccídios por apresentarem oocistos sem esporocistos e presença de quatro esporozoítos, formação de um vacúolo parasitóforo na superfície da célula, além de ocorrência de auto-infecção por merozoítos de 1ª geração e pela excistação, dentro do hospedeiro, de oocistos de parede fina; há também produção de oocistos de parede espessa que são eliminados já esporulados, no meio ambiente, juntamente com as fezes (BOROWSKI et al, 2008).…”

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Avaliação clínica, sorológica e parasitológica de serpentes naturalmente infectadas com Cryptosporidium serpentis

Paiva¹

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DEDICATÓRIADedico este trabalho... Aos meus familiaresPai e esposa, mãe (in memorian), irmãos e sobrinha.Por permitirem que eu seguisse meus caminhos sem contestação e oferecendo-me apoio, palavras e sorrisos. Aos amigos que me incentivaram nos momentos de incertezasA Letícia e toda família BeccariPor me acolherem e me oferecerem uma segunda família.A todos aqueles que estendem suas mãos Seja para oferecer, para aceitar, para ajudar ou tão somente agradecer. A infecção por Cryptosporidium serpentis é uma das enfermidades mais importantes em répteis e se caracteriza por infecção crônica, clínica ou subclínica, e presença de gastrite hipertrófica severa, regurgitação, perda de peso progressiva, mortalidade eventual e eliminação contínua e intermitente de oocistos em fezes. O objetivo deste estudo foi padronizar um teste imunoenzimático (ELISA) indireto para detecção de anticorpos contra C. serpentis, e acompanhar a evolução clínica, parasitológica e da resposta imune humoral em serpentes naturalmente infectadas com C. serpentis. Humoral immune response was observed in most animals, however, fluctuating antibodies levels with rotation of positive and negative results were observed in some snakes. AGRADECIMENTOS

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Active invasion and/or encapsulation? A reappraisal of host-cell parasitism by Cryptosporidium

Cited by 59 publications

References 57 publications

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA–RON2 pair

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA–RON2 pair

Echinococcus,GiardiaandCryptosporidium: observational studies challenging accepted dogma

Avaliação clínica, sorológica e parasitológica de serpentes naturalmente infectadas com Cryptosporidium serpentis

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