Pantothenate and CoA biosynthesis in Apicomplexa and their promise as antiparasitic drug targets.

The Apicomplexa phylum comprises thousands of distinct intracellular parasite species, including coccidians, haemosporidians, piroplasms, and cryptosporidia. These parasites are characterized by complex and divergent life cycles occupying a variety of host niches. Consequently, they exhibit distinct adaptations to the differences in nutritional availabilities, either relying on biosynthetic pathways or by salvaging metabolites from their host. Pantothenate (Pan, vitamin B5) is the precursor for the synthesis of an essential cofactor, coenzyme A (CoA), but among the apicomplexans, only the coccidian subgroup has the ability to synthesize Pan. While the pathway to synthesize CoA from Pan is largely conserved across all branches of life, there are differences in the redundancy of enzymes and possible alternative pathways to generate CoA from Pan. Impeding the scavenge of Pan and synthesis of Pan and CoA have been long recognized as potential targets for antimicrobial drug development, but in order to fully exploit these critical pathways, it is important to understand such differences. Recently, a potent class of pantothenamides (PanAms), Pan analogs, which target CoA-utilizing enzymes, has entered antimalarial preclinical development. The potential of PanAms to target multiple downstream pathways make them a promising compound class as broad antiparasitic drugs against other apicomplexans. In this review, we summarize the recent advances in understanding the Pan and CoA biosynthesis pathways, and the suitability of these pathways as drug targets in Apicomplexa, with a particular focus on the cyst-forming coccidian, Toxoplasma gondii, and the haemosporidian, Plasmodium falciparum.

Molecular phylogeny and new light microscopic data of Metchnikovella spiralis (Microsporidia: Metchnikovellidae), a hyperparasite of eugregarine Polyrhabdina sp. from the polychaete Pygospio elegans.

Metchnikovellids are a deep-branching group of microsporidia, parasites of gregarines inhabiting the alimentary tract of polychaetes and some other invertebrates. The diversity and phylogeny of these hyperparasites remain poorly studied. Modern descriptions and molecular data are still lacking for many species. The results of a light microscopy study and molecular data for Metchnikovella spiralis Sokolova et al., 2014, a hyperparasite of the eugregarine Polyrhabdina sp., isolated from the polychaete Pygospio elegans, were obtained. The original description of M. spiralis was based primarily on the analysis of stained preparations and transmission electron microscopy images. Here, the species description was complemented with the results of in vivo observations and phylogenetic analysis based on the SSU rRNA gene. It was shown that in this species, free sporogony precedes sac-bound sporogony, as it occurs in the life cycle of most other metchnikovellids. Spore sacs are entwined with spirally wound cords, and possess only one polar plug. Phylogenetic analyses did not group M. spiralis with M. incurvata, another metchnikovellid from the same gregarine species, but placed it as a sister branch to Amphiacantha. The paraphyletic nature of the genus Metchnikovella was discussed. The taxonomic summary for M. spiralis was emended.

Parasitism as a lifestyle: Ultimate intimacy between Apicomplexan protozoans and metazoan hosts.

Editorial: The Apicomplexa parasite Toxoplasma gondii glides on substrate with a helical path and releases material that forms a trail behind. The helical microtubules (green) periodically compress and relax, acting as spring force by coupling with the myosin motor (red).

Primeira descrição de pseudoparasitismo por esporocistos de Monocystis sp. em tatu-galinha, Dasypus novemcinctus (Linnaeus, 1758) - relato de caso / First description of pseudoparasitism by sporocysts of Monocystis sp. in nine banded armadillo, Dasypus novemcinctus (Linnaeus, 1758) - case report

O presente artigo é um relato sobre uma fêmea de D. novemcinctus que foi capturada de forma imprevista, durante um projeto de avaliação sanitária de animais silvestres sinantrópicos do município de Toledo/PR (autorização Sisbio/Ibama n. 55109-1). Durante a avaliação física, amostras de fezes foram coletadas após defecação espontânea e encaminhadas para análise. O material foi submetido aos métodos de flutuação simples em solução hipersaturada de cloreto de sódio e centrífugo-flutuação em sacarose. Na leitura das lâminas obtidas pelo método de centrífugo-flutuação em sacarose, foram observadas estruturas com comprimento de aproximadamente 10µm, forma bicônica e um tampão em cada extremidade, compatíveis com esporocistos de Monocystis sp. Protozoários do filo Apicomplexa, os Monocystis sp., são geralmente parasitas de anelídeos, como as minhocas. Esse organismo é comumente correlato a pseudoparasitismo em vários animais, porém não foram encontrados relatos de pseudoparasitismo desse agente em tatus-galinhas, logo essa é a primeira descrição de Monocystis sp. em espécime de D. novemcinctus.(AU)

The present article is an account of a female of D. novemcinctus which was captured during a sanitary evaluation project of synanthropic wild animals of the municipality of Toledo/PR (license SISBIO/ICMBIO n°. 55109-1). During a physical evaluation, samples of feces were collected, after spontaneous defecation, and sent for analysis. The material was subjected to simple flotation methods in hypersaturated sodium chloride solution and centrifugal-flotation solutions in sucrose. In a test reading by the centrifugal-flotation method in sucrose, structures with approximately 10µm, biconical shape and one plate at each end were observed, compatible with sporocysts of Monocystis sp. Protozoa of the phylum Apicomplexa, like Monocystis sp., it is common parasitic annelids, such as worms. This organism is a correlate of pseudoparasitism in several animals but was not found to describe this product as an agent in nine banded armadillos, so this is a first description of Monocystis sp. in specimen of D. novemcinctus.(AU)

Parasitism by Nematopsis sp. (Apicomplexa: Eugregarinida) in Mytella guyanensis at the Marine Extractive Reserve Baía do Iguape, Bahia, Brazil / Parasitismo por Nematopsis sp. (Apicomplexa: Eugregarinida) em Mytella guyanensis na Reserva Extrativista Marinha Baía do Iguape, Bahia, Brasil

Several studies show the presence of protozoa of the genus Nematopsis Schneider, 1892, in many species of bivalves. The pathogenicity of this Apicomplexa is still much debated, which is possibly related to the parasitism degree and host habitat. In this context, this study investigated parasitism by Nematopsis sp. in Mytella guyanensis (Bivalvia: Mytilidae) in a mangrove of the Marine Extractive Reserve Baía do Iguape, Bahia, Brazil. The collections were made monthly, from March 2014 to March 2015, consisting of 30 adults with shell height above 40 mm per month, totaling 360 specimens. The specimens were measured, weighed, opened, and macroscopically examined for identifying parasites and/or signs of morphological changes. After that, they were fixed in Davidson's solution and processed according to classical histological techniques, with inclusion in paraffin, obtaining 5 µm-thick sections by microtomy, and stained by Harris' Hematoxylin and Eosin (HE). The water temperature ranged from 25.5 to 33.6 ºC and the salinity from 21.1 to 34.3 Practical Salinity Units (PSU). The specimens measured between 41.1 and 68.6 mm and had an average weight of 7.24 g. Macroscopically, there was no presence of the parasite or any morphological changes related its presence. The frequency percentage of Nematopsis sp. was 99.45%. The mantle was the organ with the highest frequency of infection (46.26%), followed by the gonads (18.36%). Among the analyzed organs, all presented the parasite and, in a few severely infected cases, microscopical changes were observed in the mantle conformation. The infection intensity for most of the sessions analyzed was 1 to 3 oocysts/phagocyte; however, in one of the sessions, 9 oocysts/phagocytes were recorded. The parasite had a negative correlation with salinity. The high frequency of Nematopsis sp. should be considered for the sustainability of natural stocks, especially if such parasitism occurs simultaneously with other pathogens and stressful environmental conditions.(AU)

Diversos estudos evidenciam a presença de protozoários do gênero Nematopsis Schneider, 1892 em várias espécies de bivalves. A patogenicidade desse apicomplexo ainda é bastante debatida, a qual possivelmente relaciona-se ao grau de parasitismo e habitat do hospedeiro. Nesse contexto, este estudo investigou o parasitismo por Nematopsis sp. em Mytellaguyanensis(Bivalvia: Mytilidae) em um manguezal da Reserva Extrativista Marinha Baía do Iguape, Bahia, Brasil. As coletas foram efetuadas mensalmente, de março de 2014 a março de 2015, constando 30 adultos com altura da concha acima de 40 mm, totalizando 360 espécimens. Os espécimens foram medidos, pesados, abertos e examinados macroscopicamente para a identificação de parasitos e/ou sinais de alterações morfológicas, em seguida fixados em solução de Davidson e processados segundo técnica histológica clássica, com inclusão em parafina, obtenção de cortes de 5 µm de espessura por microtomia e coloração por hematoxilina de Harris e Eosina (HE). A temperatura da água variou de 25,5 a 33,6 ºC e a salinidade de 21,1 a 34,3 Unidades Práticas de Salinidade (UPS). Os espécimens mediram entre 41,1 e 68,6 mm e tiveram um peso médio de 7,24g. Macroscopicamente, não se observou presença do parasito ou qualquer alteração morfológica relacionada à presença do mesmo. A frequência percentual de Nematopsis sp. foi de 99,45%. O manto foi o órgão de maior frequência de infecção (46,26%), seguido das gônadas (18,36%). Entre os órgãos analisados, todos apresentaram o parasito, sendo que, para poucos casos severamente infectados, observaram-se microscopicamente modificações na conformação do manto. A intensidade de infecção para a maioria das sessões analisadas foi de 1 a 3 oocistos/fagócitos, contudo em uma das sessões foram registrados 9 oocistos/fagócitos. O parasito apresentou correlação negativa com a salinidade. A elevada frequência do Nematopsis sp. deve ser levada em consideração para a sustentabilidade dos estoques naturais, principalmente se tal parasitismo ocorrer simultaneamente a outros patógenos e condições ambientais estressantes.(AU)

Dynamics of avian haemosporidian assemblages through millennial time scales inferred from insular biotas of the West Indies.

Although introduced hemosporidian (malaria) parasites (Apicomplexa: Haemosporida) have hastened the extinction of endemic bird species in the Hawaiian Islands and perhaps elsewhere, little is known about the temporal dynamics of endemic malaria parasite populations. Haemosporidian parasites do not leave informative fossils, and records of population change are lacking beyond a few decades. Here, we take advantage of the isolation of West Indian land-bridge islands by rising postglacial sea levels to estimate rates of change in hemosporidian parasite assemblages over a millennial time frame. Several pairs of West Indian islands have been connected and separated by falling and rising sea levels associated with the advance and retreat of Pleistocene continental glaciers. We use island isolation following postglacial sea-level rise, ca. 2.5 ka, to characterize long-term change in insular assemblages of hemosporidian parasites. We find that assemblages on formerly connected islands are as differentiated as assemblages on islands that have never been connected, and both are more differentiated than local assemblages sampled up to two decades apart. Differentiation of parasite assemblages between formerly connected islands reflects variation in the prevalence of shared hemosporidian lineages, whereas differentiation between islands isolated by millions of years reflects replacement of hemosporidian lineages infecting similar assemblages of avian host species.

Apicomplexa-specific tRip facilitates import of exogenous tRNAs into malaria parasites.

The malaria-causing Plasmodium parasites are transmitted to vertebrates by mosquitoes. To support their growth and replication, these intracellular parasites, which belong to the phylum Apicomplexa, have developed mechanisms to exploit their hosts. These mechanisms include expropriation of small metabolites from infected host cells, such as purine nucleotides and amino acids. Heretofore, no evidence suggested that transfer RNAs (tRNAs) could also be exploited. We identified an unusual gene in Apicomplexa with a coding sequence for membrane-docking and structure-specific tRNA binding. This Apicomplexa protein-designated tRip (tRNA import protein)-is anchored to the parasite plasma membrane and directs import of exogenous tRNAs. In the absence of tRip, the fitness of the parasite stage that multiplies in the blood is significantly reduced, indicating that the parasite may need host tRNAs to sustain its own translation and/or as regulatory RNAs. Plasmodium is thus the first example, to our knowledge, of a cell importing exogenous tRNAs, suggesting a remarkable adaptation of this parasite to extend its reach into host cell biology.

Alveolate mitochondrial metabolic evolution: dinoflagellates force reassessment of the role of parasitism as a driver of change in apicomplexans.

Mitochondrial metabolism is central to the supply of ATP and numerous essential metabolites in most eukaryotic cells. Across eukaryotic diversity, however, there is evidence of much adaptation of the function of this organelle according to specific metabolic requirements and/or demands imposed by different environmental niches. This includes substantial loss or retailoring of mitochondrial function in many parasitic groups that occupy potentially nutrient-rich environments in their metazoan hosts. Infrakingdom Alveolata comprises a well-supported alliance of three disparate eukaryotic phyla-dinoflagellates, apicomplexans, and ciliates. These major taxa represent diverse lifestyles of free-living phototrophs, parasites, and predators and offer fertile territory for exploring character evolution in mitochondria. The mitochondria of apicomplexan parasites provide much evidence of loss or change of function from analysis of mitochondrial protein genes. Much less, however, is known of mitochondrial function in their closest relatives, the dinoflagellate algae. In this study, we have developed new models of mitochondrial metabolism in dinoflagellates based on gene predictions and stable isotope labeling experiments. These data show that many changes in mitochondrial gene content previously only known from apicomplexans are found in dinoflagellates also. For example, loss of the pyruvate dehydrogenase complex and changes in tricarboxylic acid (TCA) cycle enzyme complement are shared by both groups and, therefore, represent ancestral character states. Significantly, we show that these changes do not result in loss of typical TCA cycle activity fueled by pyruvate. Thus, dinoflagellate data show that many changes in alveolate mitochondrial metabolism are independent of the major lifestyle changes seen in these lineages and provide a revised view of mitochondria character evolution during evolution of parasitism in apicomplexans.

Protein palmitoylation and pathogenesis in apicomplexan parasites.

Apicomplexan parasites comprise a broad variety of protozoan parasites, including Toxoplasma gondii, Plasmodium, Eimeria, and Cryptosporidium species. Being intracellular parasites, the success in establishing pathogenesis relies in their ability to infect a host-cell and replicate within it. Protein palmitoylation is known to affect many aspects of cell biology. Furthermore, palmitoylation has recently been shown to affect important processes in T. gondii such as replication, invasion, and gliding. Thus, this paper focuses on the importance of protein palmitoylation in the pathogenesis of apicomplexan parasites.

[Three species of gregarines (apicomplexa: eugregarinorida) observed in the annelid polychaete Marphysa sangunea (montagu, 1815) in the lake of Tunis]. / Presence de trois espèces de grégarines (apicomplexa: eugregarinorida) chez l'Annélide polychete marphysa sanguinea (montagu, 1815) dans le lac de Tunis.

Three species of gregarines were found in specimens of the annelid polychaete Marphysa sanguinea collected in the Lake of Tunis: Bhatiella marphysae Setna, 1931, described from Marphysa sanguinea (India); Ferraria cornucephala iwamusi H. Hoshide, 1956, found in Marphysa iwamusi (Japan); and Viviera sp. a species sharing characteristics with Viviera marphysae Schrével, 1963, described in France from Marphysa sanguinea. These gregarines are reported for the first time from this host in Tunisia. Bhatiella marphysae and Viviera sp. belong to the family Lecudinidae (Aseptatorina). Our observations confirm the occurrence of a true septum in Ferraria cornucephala which must be maintained in Polyrhabdinae (Septatorina).

Apicomplexa, trypanosoma and parasitic nematode protein kinases as antiparasitic therapeutic targets.

Parasitic infections caused by Plasmodium, Trypanosoma, Leishmania, Toxoplasma and parasitic nematodes affect hundreds of millions of individuals worldwide and are the cause of significant mortality and morbidity, particularly in developing countries. These diseases also have an impact on individuals from developed countries; for example, some US troops in Iraq and Afghanistan have been infected with Leishmania. The annual mortality associated with parasitic infections is estimated to be 1.5 million deaths. The socioeconomic impact of the morbidity associated with parasitic infections is significant, and the development of new drugs, aimed at novel targets, is urgently needed to develop effective treatments for these diseases. The small-molecule inhibitors discussed in this review constitute useful tools with which to explore the relevance of kinase inhibition in inducing antiparasitic activity. The aim of recent target-based approaches used in the development of parasite kinase inhibitors is to identify novel antiparasitic agents with therapeutic potential.

Deciphering the ubiquitin-mediated pathway in apicomplexan parasites: a potential strategy to interfere with parasite virulence.

BACKGROUND: Reversible modification of proteins through the attachment of ubiquitin or ubiquitin-like modifiers is an essential post-translational regulatory mechanism in eukaryotes. The conjugation of ubiquitin or ubiquitin-like proteins has been demonstrated to play roles in growth, adaptation and homeostasis in all eukaryotes, with perturbation of ubiquitin-mediated systems associated with the pathogenesis of many human diseases, including cancer and neurodegenerative disorders. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the use of an HMM search of functional Pfam domains found in the key components of the ubiquitin-mediated pathway necessary to activate and reversibly modify target proteins in eight apicomplexan parasitic protozoa for which complete or late-stage genome projects exist. In parallel, the same search was conducted on five model organisms, single-celled and metazoans, to generate data to validate both the search parameters employed and aid paralog classification in Apicomplexa. For each of the 13 species investigated, a set of proteins predicted to be involved in the ubiquitylation pathway has been identified and demonstrates increasing component members of the ubiquitylation pathway correlating with organism and genome complexity. Sequence homology and domain architecture analyses facilitated prediction of apicomplexan-specific protein function, particularly those involved in regulating cell division during these parasite's complex life cycles. CONCLUSIONS/SIGNIFICANCE: This study provides a comprehensive analysis of proteins predicted to be involved in the apicomplexan ubiquitin-mediated pathway. Given the importance of such pathway in a wide variety of cellular processes, our data is a key step in elucidating the biological networks that, in part, direct the pathogenicity of these parasites resulting in a massive impact on global health. Moreover, apicomplexan-specific adaptations of the ubiquitylation pathway may represent new therapeutic targets for much needed drugs against apicomplexan parasites.

Studies on three species of the genus Cystocephalus Schneider, 1886 (Apicomplexa: Eugregarinida: Stylocephalidae) with special reference to host specificity and distribution of members of family Stylocephalidae in Egypt.

Three species belonging to genus Cystocephalus, Schneider 1886 were found parasitizing three coleoptra hosts. Out of 105 Blaps polychresta, only one male was infected with C. algerianus and females were parasites free. Ten percent of examined Pimelia angulata Ten percent of examined Pimelia angulata (n = 30) were infected with the same parasite. Among are one male (5.56%) and 2 females (16.67%). Out of 126 of Trachyderma hispida 6 (4.76%) were parasitized by C. gabei. Only 3 males (5.1%) and 3 females (4.48%) were harbouring this parasite. Cystocephalus albrechti were found infecting 78 (61.9%) out of 126 of T. hispida. Forty six males (77.93%) and 32 females (47.76%) were infected. Males of the three tenebrionid hosts were more susceptible to infection rather than females. B. polychresta was considered a new host for C. algerianus in Egypt. Also, C. albrechti might be considered as specific host for T. hispida. Mid and hind gut appeared blackened in case of massive infection (> 240 parasites per host) of parasitized males of C. albrechti. The host specificity and the first biogeographical map fort distribution of stylocephalids and cystocephalids are provided here.

Fatty acid biosynthesis as a drug target in apicomplexan parasites.

Apicomplexan parasitic diseases impose devastating impacts on much of the world's population. The increasing prevalence of drug resistant parasites and the growing number of immuno-compromised individuals are exacerbating the problem to the point that the need for novel, inexpensive drugs is greater now than ever. Discovery of a prokaryotic, Type II fatty acid synthesis (FAS) pathway associated with the plastid-like organelle (apicoplast) of Plasmodium and Toxoplasma has provided a wealth of novel drug targets. Since this pathway is both essential and fundamentally different from the cytosolic Type I pathway of the human host, apicoplast FAS has tremendous potential for the development of parasite-specific inhibitors. Many components of this pathway are already the target for existing antibiotics and herbicides, which should significantly reduce the time and cost of drug development. Continuing interest--both in the pharmaceutical and herbicide industries--in fatty acid synthesis inhibitors proffers an ongoing stream of potential new anti-parasitic compounds. It has now emerged that not all apicomplexan parasites have retained the Type II fatty acid biosynthesis pathway. No fatty acid biosynthesis enzymes are encoded in the genome of Theileria annulata or T. parva, suggesting that fatty acid synthesis is lacking in these parasites. The human intestinal parasite Cryptosporidium parvum appears to have lost the apicoplast entirely; instead relying on an unusual cytosolic Type I FAS. Nevertheless, newly developed anti-cancer and anti-obesity drugs targeting human Type I FAS may yet prove efficacious against Cryptosporidium and other apicomplexans that rely on this Type I FAS pathway.

Mitochondrial drug targets in apicomplexan parasites.

In evolutionary terms, mitochondria in apicomplexan parasites appear to be "relicts-in-the-making": they possess the smallest mitochondrial genomes known, encoding only three proteins, and in one genus, Cryptosporidium, the genome is eliminated altogether. Several features of mitochondrial physiology provide validated or potential targets for antiparasitic drugs. Atovaquone, a broad spectrum antiparasitic drug, selectively inhibits mitochondrial electron transport at the cytochrome bc(1) complex and collapses mitochondrial membrane potential. Recent investigations using model systems provide important insights into the mechanism of action for this drug, which may prove valuable for development of other selective inhibitors of mitochondrial electron transport. Although mitochondria do not appear to be a source of ATP during the erythrocytic stages in Plasmodium species, they do serve other critical functions, including the assembly of iron-sulfur clusters and various other biosynthetic processes depending on the species. To serve these metabolic functions, parasites need to maintain the apparatus for mitochondrial genome replication, repair, recombination, transcription, and translation, components of which are encoded in the nucleus and imported into the mitochondrion. Several unusual aspects of the components of this apparatus are coming to light through genome sequence analyses, and could provide potential targets for antiparasitic drug discovery and development.

Targeting purine and pyrimidine metabolism in human apicomplexan parasites.

Synthesis de novo, acquisition by salvage and interconversion of purines and pyrimidines represent the fundamental requirements for their eventual assembly into nucleic acids as nucleotides and the deployment of their derivatives in other biochemical pathways. A small number of drugs targeted to nucleotide metabolism, by virtue of their effect on folate biosynthesis and recycling, have been successfully used against apicomplexan parasites such as Plasmodium and Toxoplasma for many years, although resistance is now a major problem in the prevention and treatment of malaria. Many targets not involving folate metabolism have also been explored at the experimental level. However, the unravelling of the genome sequences of these eukaryotic unicellular organisms, together with increasingly sophisticated molecular analyses, opens up possibilities of introducing new drugs that could interfere with these processes. This review examines the status of established drugs of this type and the potential for further exploiting the vulnerability of apicomplexan human pathogens to inhibition of this key area of metabolism.

Pyruvate : NADP+ oxidoreductase from the mitochondrion of Euglena gracilis and from the apicomplexan Cryptosporidium parvum: a biochemical relic linking pyruvate metabolism in mitochondriate and amitochondriate protists.

Most eukaryotes perform the oxidative decarboxylation of pyruvate in mitochondria using pyruvate dehydrogenase (PDH). Eukaryotes that lack mitochondria also lack PDH, using instead the O(2)-sensitive enzyme pyruvate : ferredoxin oxidoreductase (PFO), which is localized either in the cytosol or in hydrogenosomes. The facultatively anaerobic mitochondria of the photosynthetic protist Euglena gracilis constitute a hitherto unique exception in that these mitochondria oxidize pyruvate with the O(2)-sensitive enzyme pyruvate : NADP oxidoreductase (PNO). Cloning and analysis of Euglena PNO revealed that the cDNA encodes a mitochondrial transit peptide followed by an N-terminal PFO domain that is fused to a C-terminal NADPH-cytochrome P450 reductase (CPR) domain. Two independent 5.8-kb full-size cDNAs for Euglena mitochondrial PNO were isolated; the gene was expressed in cultures supplied with 2% CO(2) in air and with 2% CO(2) in N(2). The apicomplexan Cryptosporidium parvum was also shown to encode and express the same PFO-CPR fusion, except that, unlike E. gracilis, no mitochondrial transit peptide for C. parvum PNO was found. Recombination-derived remnants of PNO are conserved in the genomes of Saccharomyces cerevisiae and Schizosaccharomyces pombe as proteins involved in sulfite reduction. Notably, Trypanosoma brucei was found to encode homologs of both PFO and all four PDH subunits. Gene organization and phylogeny revealed that eukaryotic nuclear genes for mitochondrial, hydrogenosomal, and cytosolic PFO trace to a single eubacterial acquisition. These findings suggest a common ancestry of PFO in amitochondriate protists with Euglena mitochondrial PNO and Cryptosporidium PNO. They are also consistent with the view that eukaryotic PFO domains are biochemical relics inherited from a facultatively anaerobic, eubacterial ancestor of mitochondria and hydrogenosomes.

Mix and match modules: structure and function of microneme proteins in apicomplexan parasites.

Microneme organelles are found in the apical complex of all apicomplexan parasites and play an important role in the invasion process. The recent identification of microneme proteins from different apicomplexan genera has revealed a striking conservation of structural domains, some of which show functional complementation across species. This supports the idea that the mechanism of host cell invasion across the phylum is conserved not only morphologically, but also functionally at the molecular level. Here, we review and summarize these recent findings.