| a highly infectious plasmodium yoelii parasite, bearing plasmodium falciparum circumsporozoite protein. | plasmodium circumsporozoite protein (csp) is a major surface antigen present in the sporozoite (spz) stage of a malaria parasite. rts, s vaccine, the most clinically advanced malaria vaccine, consists of a large portion of plasmodium falciparum csp (pfcsp). a highly infectious, recombinant rodent malaria, plasmodium yoelii parasite bearing a full-length pfcsp, pfcsp/py spz, was needed as a tool to evaluate the role of pfcsp in mediating, protective, anti-malaria immunity in a mouse model. | 2016 | 27068454 |
| the tlr2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development. | tlrs (toll-like receptors) play an important role in the initiation of innate immune responses against invading microorganisms. although several tlrs have been reported to be involved in the innate immune response against the blood-stage of malaria parasites, the role of tlrs in the development of the pre-erythrocytic stage is still largely unknown. here, we found that sporozoite and its lysate could significantly activate the tlr2, and induce macrophages to release proinflammatory cytokines, in ... | 2015 | 26667391 |
| co-expression of interleukin-15 enhances the protective immune responses induced by immunization with a murine malaria mva-based vaccine encoding the circumsporozoite protein. | malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. although the most advanced candidate malaria vaccine (rts,s) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of rts,s immunization (when used alone) on global malaria transmission. here we describe the development and characterization of a novel modified vaccinia virus ankara (mva)-based malaria vaccine which co-expresses th ... | 2015 | 26505634 |
| plasmodium yoelii inhibitor of cysteine proteases is exported to exomembrane structures and interacts with yoelipain-2 during asexual blood-stage development. | plasmodium falciparum (pf) blood stages express falstatin, an inhibitor of cysteine proteases (icp), which is implicated in regulating proteolysis during red blood cell infection. recent data using the plasmodium berghei rodent malaria model suggested an additional role for icp in the infection of hepatocytes by sporozoites and during liver-stage development. here we further characterize the role of icp in vivo during infection with plasmodium yoelii (py) and pf. we found that py-icp was refract ... | 2013 | 23421981 |
| perturbations of plasmodium puf2 expression and rna-seq of puf2-deficient sporozoites reveal a critical role in maintaining rna homeostasis and parasite transmissibility. | malaria's cycle of infection requires parasite transmission between a mosquito vector and a mammalian host. we here demonstrate that the plasmodium yoelii pumilio-fbf family member puf2 allows the sporozoite to remain infectious in the mosquito salivary glands while awaiting transmission. puf2 mediates this solely through its rna-binding domain (rbd) likely by stabilizing or hastening the degradation of specific mrnas. puf2 traffics to sporozoite cytosolic granules, which are negative for severa ... | 2013 | 23356439 |
| immunogenicity, protective efficacy and safety of a recombinant dna vaccine encoding truncated plasmodium yoelii sporozoite asparagine-rich protein 1 (pysap1). | although great efforts have been undertaken for the development of malaria vaccines, no completely effective malaria vaccines are available yet. despite being clinically silent, the pre-erythrocytic stage is considered an ideal target for the development of malaria vaccines. sporozoite asparagine-rich protein 1 (sap1) is a sporozoite-localized protein that regulates the expression of uis (upregulated in infectious sporozoites) genes, which are essential for the infectivity of sporozoites. in thi ... | 2013 | 23357857 |
| total and putative surface proteomics of malaria parasite salivary gland sporozoites. | malaria infections of mammals are initiated by the transmission of plasmodium salivary gland sporozoites during an anopheles mosquito vector bite. sporozoites make their way through the skin and eventually to the liver, where they infect hepatocytes. blocking this initial stage of infection is a promising malaria vaccine strategy. therefore, comprehensively elucidating the protein composition of sporozoites will be invaluable in identifying novel targets for blocking infection. previous efforts ... | 2013 | 23325771 |
| quantification of sporozoite invasion, migration, and development by microscopy and flow cytometry. | there is an important role for in vitro assays to better understand the initial steps of malaria infection. in this section, we describe both microscopy-based and flow cytometry-based sporozoite invasion, migration and development assays with the rodent malaria parasites, plasmodium berghei and plasmodium yoelii, and the human malaria parasite, plasmodium falciparum. | 0 | 22990793 |
| a class of tricyclic compounds blocking malaria parasite oocyst development and transmission. | malaria is a deadly infectious disease in many tropical and subtropical countries. previous efforts to eradicate malaria have failed, largely due to the emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in particular, the lack of drugs or vaccines to block parasite transmission. atp-binding cassette (abc) transporters are known to play a role in drug transport, metabolism, and resistance in many organisms, including malaria parasites. to investigate whether a plasmodiu ... | 2012 | 23129054 |
| skin-draining lymph node priming is sufficient to induce sterile immunity against pre-erythrocytic malaria. | the plasmodium-infected hepatocyte has been considered necessary to prime the immune responses leading to sterile protection after vaccination with attenuated sporozoites. however, it has recently been demonstrated that priming also occurs in the skin. we wished to establish if sterile protection could be obtained in the absence of priming by infected hepatocytes. to this end, we developed a subcutaneous (s.c.) immunization protocol where few, possibly none, of the immunizing irradiated plasmodi ... | 2012 | 23255300 |
| a rapid and scalable density gradient purification method for plasmodium sporozoites. | malaria remains a major human health problem, with no licensed vaccine currently available. malaria infections initiate when infectious plasmodium sporozoites are transmitted by anopheline mosquitoes during their blood meal. investigations of the malaria sporozoite are, therefore, of clear medical importance. however, sporozoites can only be produced in and isolated from mosquitoes, and their isolation results in large amounts of accompanying mosquito debris and contaminating microbes. | 2012 | 23244590 |
| hiv nonnucleoside reverse transcriptase inhibitors and trimethoprim-sulfamethoxazole inhibit plasmodium liver stages. | although nonnucleoside reverse transcriptase inhibitors (nnrtis) are usually part of first-line treatment regimens for human immunodeficiency virus (hiv), their activity on plasmodium liver stages remains unexplored. additionally, trimethoprim-sulfamethoxazole (tmp-smx), used for opportunistic infection prophylaxis in hiv-exposed infants and hiv-infected patients, reduces clinical episodes of malaria; however, tmp-smx effect on plasmodium liver stages requires further study. | 0 | 23125449 |
| a nonintegrative lentiviral vector-based vaccine provides long-term sterile protection against malaria. | trials testing the rts,s candidate malaria vaccine and radiation-attenuated sporozoites (ras) have shown that protective immunity against malaria can be induced and that an effective vaccine is not out of reach. however, longer-term protection and higher protection rates are required to eradicate malaria from the endemic regions. it implies that there is still a need to explore new vaccine strategies. lentiviral vectors are very potent at inducing strong immunological memory. however their integ ... | 2012 | 23133649 |
| extrahepatic exoerythrocytic forms of rodent malaria parasites at the site of inoculation: clearance after immunization, susceptibility to primaquine, and contribution to blood-stage infection. | plasmodium sporozoites are inoculated into the skin of the mammalian host as infected mosquitoes probe for blood. a proportion of the inoculum enters the bloodstream and goes to the liver, where the sporozoites invade hepatocytes and develop into the next life cycle stage, the exoerythrocytic, or liver, stage. here, we show that a small fraction of the inoculum remains in the skin and begins to develop into exoerythrocytic forms that can persist for days. skin exoerythrocytic forms were observed ... | 2012 | 22431651 |
| adjuvant-like effect of vaccinia virus 14k protein: a case study with malaria vaccine based on the circumsporozoite protein. | development of subunit vaccines for malaria that elicit a strong, long-term memory response is an intensive area of research, with the focus on improving the immunogenicity of a circumsporozoite (cs) protein-based vaccine. in this study, we found that a chimeric protein, formed by fusing vaccinia virus protein 14k (a27) to the cs of plasmodium yoelii, induces strong effector memory cd8(+) t cell responses in addition to high-affinity abs when used as a priming agent in the absence of any adjuvan ... | 2012 | 22615208 |
| vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing cs of plasmodium. | with the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (ppv-vlps) carrying the cd8(+) t cell epitope (syvpsaeqi) of the circumsporozoite (cs) protein from plasmodium yoelii fused to the ppv vp2 capsid protein (ppv-pycs), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. as a proof-of concept, we have characterized the anti-cs cd8(+) t cell response elicited by these h ... | 2012 | 22529915 |
| a hybrid multistage protein vaccine induces protective immunity against murine malaria. | we have previously reported the design and expression of chimeric recombinant proteins as an effective platform to deliver malaria vaccines. the erythrocytic and exoerythrocytic protein chimeras described included autologous t helper epitopes genetically linked to defined b cell epitopes. proof-of-principle studies using vaccine constructs based on the plasmodium yoelii circumsporozoite protein (csp) and p. yoelii merozoite surface protein-1 (msp-1) showed encouraging results when tested individ ... | 2012 | 22252877 |
| plasmodium yoelii macrophage migration inhibitory factor is necessary for efficient liver-stage development. | mammalian macrophage migration inhibitory factor (mif) is a multifaceted cytokine involved in both extracellular and intracellular functions. malaria parasites express a mif homologue that might modulate host immune responses against blood-stage parasites, but the potential importance of mif against other life cycle stages remains unstudied. in this study, we characterized the mif homologue of plasmodium yoelii throughout the life cycle, with emphasis on preerythrocytic stages. p. yoelii mif (py ... | 2012 | 22252874 |
| probucol-induced α-tocopherol deficiency protects mice against malaria infection. | the emergence of malaria pathogens having resistance against antimalarials implies the necessity for the development of new drugs. recently, we have demonstrated a resistance against malaria infection of α-tocopherol transfer protein knockout mice showing undetectable plasma levels of α-tocopherol, a lipid-soluble antioxidant. however, dietary restriction induced α-tocopherol deficiency is difficult to be applied as a clinical antimalarial therapy. here, we report on a new strategy to potentiall ... | 2015 | 26296197 |
| colocalization of a cd1d-binding glycolipid with a radiation-attenuated sporozoite vaccine in lymph node-resident dendritic cells for a robust adjuvant effect. | a cd1d-binding glycolipid, α-galactosylceramide (αgalcer), activates invariant nk t cells and acts as an adjuvant. we previously identified a fluorinated phenyl ring-modified αgalcer analog, 7dw8-5, displaying nearly 100-fold stronger cd1d binding affinity. in the current study, 7dw8-5 was found to exert a more potent adjuvant effect than αgalcer for a vaccine based on radiation-attenuated sporozoites of a rodent malaria parasite, plasmodium yoelii, also referred to as irradiated p. yoelii sporo ... | 2015 | 26254338 |
| l-arginine supplementation in mice enhances no production in spleen cells and inhibits plasmodium yoelii transmission in mosquitoes. | the life cycle of plasmodium is complex, requiring invasion of two different hosts, humans and mosquitoes. in humans, initiation of an effective th1 response during early infection is critical for the control of parasite multiplication. in mosquitoes, inhibition of the development of sexual-stage parasites interrupts the parasite transmission. in this study, we aim to investigate whether dietary supplementation of l-arginine (l-arg) in mice affects plasmodium yoelii 17xl (py17xl) transmission in ... | 2015 | 26070945 |
| mechanisms of stage-transcending protection following immunization of mice with late liver stage-arresting genetically attenuated malaria parasites. | malaria, caused by plasmodium parasite infection, continues to be one of the leading causes of worldwide morbidity and mortality. development of an effective vaccine has been encumbered by the complex life cycle of the parasite that has distinct pre-erythrocytic and erythrocytic stages of infection in the mammalian host. historically, malaria vaccine development efforts have targeted each stage in isolation. an ideal vaccine, however, would target multiple life cycle stages with multiple arms of ... | 2015 | 25974076 |
| chloroquine neither eliminates liver stage parasites nor delays their development in a murine chemoprophylaxis vaccination model. | chemoprophylaxis vaccination (cvac) confers long lasting sterile protection against homologous parasite strains in humans, and involves inoculation of infectious sporozoites (spz) under drug cover. cvac using the drug chloroquine (cq) induces pre-erythrocytic immunity in humans that includes antibody to spz and t-cell responses to liver stage (ls) parasites. the mechanism by which cvac with cq induces strong protective immunity is not understood as untreated infections do not confer protection. ... | 2015 | 25914686 |
| cyclic gmp balance is critical for malaria parasite transmission from the mosquito to the mammalian host. | transmission of malaria occurs during anopheles mosquito vector blood meals, when plasmodium sporozoites that have invaded the mosquito salivary glands are delivered to the mammalian host. sporozoites display a unique form of motility that is essential for their movement across cellular host barriers and invasion of hepatocytes. while the molecular machinery powering motility and invasion is increasingly well defined, the signaling events that control these essential parasite activities have not ... | 2015 | 25784701 |
| regulation of plasmodium yoelii oocyst development by strain- and stage-specific small-subunit rrna. | one unique feature of malaria parasites is the differential transcription of structurally distinct rrna (rrna) genes at different developmental stages: the a-type genes are transcribed mainly in asexual stages, whereas the s-type genes are expressed mostly in sexual or mosquito stages. conclusive functional evidence of different rrnas in regulating stage-specific parasite development, however, is still absent. here we performed genetic crosses of plasmodium yoelii parasites with one parent havin ... | 2015 | 25759501 |
| a sufficient role of mhc class i molecules on hepatocytes in anti-plasmodial activity of cd8 (+) t cells in vivo. | although cd8(+) t cells are shown to mediate the protective immunity against the liver stages of malaria parasites in mice, whether the direct presentation of malaria antigen by major histocompatibility complex (mhc) class i molecules expressed on the liver of infected host is required for anti-plasmodial activity of cd8(+) t cells is still unknown. presently, there is only one cd8(+) epitope, syvpsaeqi, derived from the circumsporozoite protein of plasmodium yoelii (pycs), that mediates anti-ma ... | 2015 | 25729379 |
| within-host competition does not select for virulence in malaria parasites; studies with plasmodium yoelii. | in endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. it has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. this competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. it has also been a ... | 2015 | 25658331 |
| cd40 is required for protective immunity against liver stage plasmodium infection. | the costimulatory molecule cd40 enhances immunity through several distinct roles in t cell activation and t cell interaction with other immune cells. in a mouse model of immunity to liver stage plasmodium infection, cd40 was critical for the full maturation of liver dendritic cells, accumulation of cd8(+) t cells in the liver, and protective immunity induced by immunization with the plasmodium yoelii fabb/f(-) genetically attenuated parasite. using mixed adoptive transfers of polyclonal wild-typ ... | 2015 | 25646303 |
| interactions between a fungal entomopathogen and malaria parasites within a mosquito vector. | mosquitoes are becoming increasingly resistant to the chemical insecticides currently available for malaria vector control, spurring interest in alternative management tools. one promising technology is the use of fungal entomopathogens. fungi have been shown to impact the potential for mosquitoes to transmit malaria by reducing mosquito longevity and altering behaviour associated with flight and host location. additionally, fungi could impact the development of malaria parasites within the mosq ... | 2015 | 25626485 |
| dried whole-plant artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin. | pharmaceutical monotherapies against human malaria have proven effective, although ephemeral, owing to the inevitable evolution of resistant parasites. resistance to two or more drugs delivered in combination will evolve more slowly; hence combination therapies have become the preferred norm in the fight against malaria. at the forefront of these efforts has been the promotion of artemisinin combination therapy, but despite these efforts, resistance to artemisinin has begun to emerge. in 2012, w ... | 2015 | 25561559 |
| immunization of mice with live-attenuated late liver stage-arresting plasmodium yoelii parasites generates protective antibody responses to preerythrocytic stages of malaria. | understanding protective immunity to malaria is essential for the design of an effective vaccine to prevent the large number of infections and deaths caused by this parasitic disease. to date, whole-parasite immunization with attenuated parasites is the most effective method to confer sterile protection against malaria infection in clinical trials. mouse model studies have highlighted the essential role that cd8(+) t cells play in protection against preerythrocytic stages of malaria; however, th ... | 2014 | 25267837 |
| ssp3 is a novel plasmodium yoelii sporozoite surface protein with a role in gliding motility. | plasmodium sporozoites develop within oocysts in the mosquito midgut wall and then migrate to the salivary glands. after transmission, they embark on a complex journey to the mammalian liver, where they infect hepatocytes. proteins on the sporozoite surface likely mediate multiple steps of this journey, yet only a few sporozoite surface proteins have been described. here, we characterize a novel, conserved sporozoite surface protein (ssp3) in the rodent malaria parasite plasmodium yoelii. ssp3 i ... | 2014 | 25156733 |
| susceptibility to plasmodium yoelii preerythrocytic infection in balb/c substrains is determined at the point of hepatocyte invasion. | after transmission by anopheles mosquitoes, plasmodium sporozoites travel to the liver, infect hepatocytes, and rapidly develop as intrahepatocytic liver stages (ls). rodent models of malaria exhibit large differences in the magnitude of liver infection, both between parasite species and between strains of mice. this has been mainly attributed to differences in innate immune responses and parasite infectivity. here, we report that balb/cbyj mice are more susceptible to plasmodium yoelii preeryth ... | 2014 | 25312960 |
| plasmodium yoelii vitamin b5 pantothenate transporter candidate is essential for parasite transmission to the mosquito. | in nearly all non-photosynthetic cells, pantothenate (vitamin b5) transport and utilization are prerequisites for the synthesis of the universal essential cofactor coenzyme a (coa). early studies showed that human malaria parasites rely on the uptake of pantothenate across the parasite plasma membrane for survival within erythrocytes. recently, a p. falciparum candidate pantothenate transporter (pat) was characterized by functional complementation in yeast. these studies revealed that pfpat medi ... | 2014 | 25012929 |
| artesunate versus chloroquine infection-treatment-vaccination defines stage-specific immune responses associated with prolonged sterile protection against both pre-erythrocytic and erythrocytic plasmodium yoelii infection. | sterile protection against malaria infection can be achieved through vaccination of mice and humans with whole plasmodium spp. parasites. one such method, known as infection-treatment-vaccination (itv), involves immunization with wild type sporozoites (spz) under drug coverage. in this work, we used the different effects of antimalarial drugs chloroquine (cq) and artesunate (as) on blood stage (bs) parasites to dissect the stage-specific immune responses in mice immunized with plasmodium yoelii ... | 2014 | 24958899 |
| apicoap: the first computational model for identifying apicoplast-targeted proteins in multiple species of apicomplexa. | most of the parasites of the phylum apicomplexa contain a relict prokaryotic-derived plastid called the apicoplast. this organelle is important not only for the survival of the parasite, but its unique properties make it an ideal drug target. the majority of apicoplast-associated proteins are nuclear encoded and targeted post-translationally to the organellar lumen via a bipartite signaling mechanism that requires an n-terminal signal and transit peptide (tp). attempts to define a consensus moti ... | 2012 | 22574192 |
| cloning, expression, purification and characterization of plasmodium spp. glyceraldehyde-3-phosphate dehydrogenase. | plasmodium spp. solely rely on glycolysis for their energy needs during asexual multiplication in human rbcs, making the enzymes of this pathway potential drug targets. we have cloned, over-expressed and purified plasmodium falciparum glyceraldehyde-3-phosphate dehydrogenase (pfgapdh) for its kinetic and structural characterization. ∼ 30-40 mg pure recombinant enzyme with a specific activity of 12.6 units/mg could be obtained from a liter of escherichia coli culture. this enzyme is a homotetrame ... | 2016 | 26341815 |
| phagosomal acidification prevents macrophage inflammatory cytokine production to malaria, and dendritic cells are the major source at the early stages of infection: implication for malaria protective immunity development. | inflammatory cytokines produced at the early stages of malaria infection contribute to shaping protective immunity and pathophysiology. to gain mechanistic insight into these processes, it is important to understand the cellular origin of cytokines because both cytokine input and cytokine-producing cells play key roles. here, we determined cytokine responses by monocytes, macrophages, and dendritic cells (dcs) to purified plasmodium falciparum and plasmodium berghei anka, and by spleen macrophag ... | 2015 | 26240140 |
| immunization of mice with plasmodium tctp delays establishment of plasmodium infection. | translationally controlled tumour protein (tctp) may play an important role in the establishment or maintenance of parasitemia in a malarial infection. in this study, the potential of tctp as a malaria vaccine was investigated in two trials. in the initial vaccine trial, plasmodium falciparum tctp (pftctp) was expressed in saccharomyces cerevisiae and used to immunize balb/c mice. following challenge with plasmodium yoelii ym, parasitemia was significantly reduced during the early stages of infe ... | 2015 | 25376500 |
| transfusion of stored blood impairs host defenses against gram-negative pathogens in mice. | although human red blood cell (rbc) units may be refrigerator stored for up to 42 days, transfusion of older rbcs acutely delivers a large bolus of iron to mononuclear phagocytes. similarly, iron dextran circulates in plasma for hours to days and is progressively cleared by mononuclear phagocytes, which return iron to plasma. finally, malaria infection continuously delivers iron to macrophages by intra- and extravascular hemolysis. studies suggest that iron administration increases infectious ri ... | 2014 | 24840185 |
| malaria-cutaneous leishmaniasis co-infection: influence on disease outcomes and immune response. | malaria and cutaneous leishmaniasis (cl) are co-endemic throughout large regions in tropical countries and co-infection may impact the evolution of host-parasite interactions. in the present study, we evaluate malaria/leishmaniasis disease outcome, th1/th2 cytokine levels and the cd4 and cd8 t-cell profiles in a co-infection murine model (balb/c) of plasmodium yoelii 17xnl (py) and leishmania amazonensis (la) or l. braziliensis (lb). malaria parasitaemia was assessed through blood strains staine ... | 2016 | 27446022 |
| listeria monocytogenes inoculation protects mice against blood-stage plasmodium yoelii infection. | listeria monocytogenes (lm) has been used as the adjuvant or vector for tumor and viral vaccine for its capability of eliciting all aspects of cell-mediated immunity including t cell activation and interferon-gamma (ifn-γ) production. these effector components play critical roles in the protection against plasmodium infection in both human malaria and mouse models. therefore, immune response induced by lm infection may benefit the defense against malaria. to test this hypothesis, we employed blo ... | 2013 | 23303295 |
| co-infection restrains litomosoides sigmodontis filarial load and plasmodial p. yoelii but not p. chabaudi parasitaemia in mice. | infection with multiple parasite species is clearly the norm rather than the exception, in animals as well as in humans. filarial nematodes and plasmodium spp. are important parasites in human public health and they are often co-endemic. interactions between these parasites are complex. the mechanisms underlying the modulation of both the course of malaria and the outcome of filarial infection are poorly understood. despite increasing activity in recent years, studies comparing co- and mono-infe ... | 2014 | 24717449 |
| plasmodium suppresses expansion of t cell responses to heterologous infections. | plasmodium remains a major pathogen causing malaria and impairing defense against other infections. defining how plasmodium increases susceptibility to heterologous pathogens may lead to interventions that mitigate the severity of coinfections. previous studies proposed that reduced t cell responses during coinfections are due to diminished recruitment of naive t cells through infection-induced decreases in chemokine ccl21. we found that, although listeria infections reduced expression of ccl21 ... | 2015 | 25505280 |
| cd8(+) t-cell-mediated immunity against malaria: a novel heterologous prime-boost strategy. | recently, a vaccine against malaria was successfully tested in a human phase iii trial. the efficacy of this vaccine formulation, based on the plasmodium falciparum circumsporozoite protein, was approximately 50% and correlated with the presence of antibodies specific to the infective stages of the malaria parasites. different strategies are being pursued to improve vaccine efficacy levels. one such strategy is the induction of specific cytotoxic t cells that can destroy the intracellular hepato ... | 2012 | 23151162 |
| actively induced antigen-specific cd8+ t cells by epitope-bearing parasite pre-infection but not prime/boost virus vector vaccination could ameliorate the course of plasmodium yoelii blood-stage infection. | the lack of mhc molecules on red blood cells (rbcs) has led to questions regarding the immunological function of cd8(+) t cells against malarial blood-stage (mbs). however, several recent reports contradicting with this concept have suggested that they play an important role in the course of mbs infection. the present study generated genetically engineered murine malaria, plasmodium yoelii, which expresses a well-defined trypanosoma cruzi-derived, h-2k(b)-restricted cd8(+) t cell epitope, anynft ... | 2012 | 22902783 |
| protein function annotation with structurally aligned local sites of activity (salsas). | the prediction of biochemical function from the 3d structure of a protein has proved to be much more difficult than was originally foreseen. a reliable method to test the likelihood of putative annotations and to predict function from structure would add tremendous value to structural genomics data. we report on a new method, structurally aligned local sites of activity (salsa), for the prediction of biochemical function based on a local structural match at the predicted catalytic or binding sit ... | 2013 | 23514271 |
| one episode of self-resolving plasmodium yoelii infection transiently exacerbates chronic mycobacterium tuberculosis infection. | malaria and tuberculosis (tb) are two of the main causes of death from infectious diseases globally. the pathogenic agents, plasmodium parasites and mycobacterium tuberculosis, are co-endemic in many regions in the world, however, compared to other co-infections like hiv/tb or helminth/tb, malaria/tb has been given less attention both in clinical and immunological studies. due to the lack of sufficient human data, the impact of malaria on tb and vice versa is difficult to estimate but co-infecti ... | 2016 | 26913029 |
| cd41 is a reliable identification and activation marker for murine basophils in the steady state and during helminth and malarial infections. | basophils, a rare leukocyte population in peripheral circulation, are conventionally identified as cd45(int) cd49b(+) fcεri(+) cells. here, we show that basophils from blood and several organs of naïve wild-type mice express cd41, the α subunit of α(iib)β₃ integrin. cd41 expression on basophils is upregulated after in vivo il-3 treatment and during infection with nippostrongylus brasiliensis (nb). moreover, cd41 can be used as a reliable marker for basophils, circumventing technical difficulties ... | 2014 | 24610714 |
| grammomys surdaster, the natural host for plasmodium berghei parasites, as a model to study whole-organism vaccines against malaria. | inbred mice are commonly used to test candidate malaria vaccines, but have been unreliable for predicting efficacy in humans. to establish a more rigorous animal model, we acquired african woodland thicket rats of the genus grammomys, the natural hosts for plasmodium berghei thicket rats were acquired and identified as grammomys surdaster by skull and teeth measurements and mitochondrial dna genotyping. herein, we demonstrate that thicket rats are highly susceptible to infection by p berghei, an ... | 2017 | 28115674 |
| detailed methodology for high resolution scanning electron microscopy (sem) of murine malaria parasitized-erythrocytes. | scanning electron microscopy (sem) is a powerful tool used to investigate object surfaces and has been widely applied in both material science and biology. with respect to the study of malaria, sem revealed that erythrocytes infected with plasmodium falciparum, a human parasite, display 'knob-like' structures on their surface comprising parasitized proteins. however, detailed methodology for sem studies of malaria parasites is lacking in the literature making such studies challenging. here, we p ... | 2016 | 26987676 |
| detection of plasmodium berghei and plasmodium yoelii liver-stage parasite burden by quantitative real-time pcr. | direct detection and quantification of liver-stage plasmodium parasites became possible with the development of quantitative real-time pcr (qpcr). here we describe the measurement of parasite burden in the livers of mice infected with the rodent malaria species, plasmodium berghei and plasmodium yoelii. this method is based on detection of expression of parasite ribosomal 18s rna and can serve as an endpoint to accurately evaluate the efficacy of vaccines targeting the preerythrocytic stages of ... | 2015 | 26450381 |
| characterization of liver cd8 t cell subsets that are associated with protection against pre-erythrocytic plasmodium parasites. | murine models of malaria, such as plasmodium berghei (pb) and plasmodium yoelii (py), have been used for decades to identify correlates of protection associated with immunization using radiation-attenuated sporozoites (ras). to date, ras is the only known immunization regimen to consistently deliver 100 % sterilizing immunity and is considered the "gold standard" of protection against malaria. the ability to isolate lymphocytes directly from the liver of immune mice has facilitated the identific ... | 2015 | 26450377 |
| dynamic control of hepatic plasmodium numbers by hepcidin despite elevated liver iron during iron supplementation. | treatment of iron deficiency anemia in malaria endemic areas is complicated as iron supplementation increases malaria risk while malaria decreases iron absorption. here we measured the influence of hepcidin expression and non-heme iron during iron supplementation on hepatic plasmodium berghei numbers in anemic and non-anemic mice. despite elevated hepatic non-heme iron on the high iron diet, elevated hepcidin expression is associated with less parasite bioavailable iron and lower hepatic parasit ... | 2016 | 26384816 |
| dendritic cells subsets mediated immune response during plasmodium berghei anka and plasmodium yoelii infection. | the roles of dendritic cells (dcs) in mediating immunity against plasmodium infection have been extensively investigated, but immune response during pathogenesis of malaria is still poorly understood. in the present study, we compared the splenic dcs phenotype and function during p. berghei anka (pba) or p. yoelii (p. yoelii) infection in swiss mice. we observed that pba-infected mice developed more myeloid and mature dcs capable of secreting il-12, while p. yoelii-infected mice had more plasmac ... | 2015 | 25792277 |
| host erythrocyte environment influences the localization of exported protein 2, an essential component of the plasmodium translocon. | malaria parasites replicating inside red blood cells (rbcs) export a large subset of proteins into the erythrocyte cytoplasm to facilitate parasite growth and survival. ptex, the parasite-encoded translocon, mediates protein transport across the parasitophorous vacuolar membrane (pvm) in plasmodium falciparum-infected erythrocytes. proteins exported into the erythrocyte cytoplasm have been localized to membranous structures, such as maurer's clefts, small vesicles, and a tubovesicular network. c ... | 2015 | 25662767 |
| in vitro alterations do not reflect a requirement for host cell cycle progression during plasmodium liver stage infection. | prior to invading nonreplicative erythrocytes, plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. while normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but i ... | 2015 | 25416236 |
| expression and localization of rhoptry neck protein 5 in merozoites and sporozoites of plasmodium yoelii. | host cell invasion by apicomplexan parasites marks a crucial step in disease establishment and pathogenesis. the moving junction (mj) is a conserved and essential feature among parasites of this phylum during host cell invasion, thus proteins that associate at this mj are potential targets of drug and vaccine development. in both toxoplasma gondii and plasmodium falciparum, a micronemal protein, apical membrane antigen 1 (ama1), and rhoptry neck proteins (rons; ron2 and ron4) form an essential c ... | 2014 | 25102354 |
| memory t cells maintain protracted protection against malaria. | immunologic memory is one of the cardinal features of antigen-specific immune responses, and the persistence of memory cells contributes to prophylactic immunizations against infectious agents. adequately maintained memory t and b cell pools assure a fast, effective and specific response against re-infections. however, many aspects of immunologic memory are still poorly understood, particularly immunologic memory inducible by parasites, for example, plasmodium spp., the causative agents of malar ... | 2014 | 24709142 |
| differential role of t regulatory and th17 in swiss mice infected with plasmodium berghei anka and plasmodium yoelii. | the outcome of malaria infection is determined, in part, by the balance of pro-inflammatory and regulatory immune responses. host immune responses in disease including malaria are finely regulated by the opposing effects of th17 and t regulatory (treg) cells. here we have examined the role of treg cells and th17 cells during malaria infection and find that low levels of treg cells possibly influence the outcome of infections with the lethal strain of plasmodium berghei anka (pba). in contrast, h ... | 2014 | 24675415 |
| alpha-tocopherol transfer protein gene inhibition enhances the acquired immune response during malaria infection in mice. | immune response to malaria infection is complex and seems to be regulated by innate and adaptive immune response as well as environmental factors such as host genetics and nutritional status. previously, we have reported that α-tocopherol transfer protein knockout (α-ttp(δ)) mice, showing low concentrations of α-tocopherol in circulation, infected with plasmodium berghei nk65 survived significantly longer as compared with the wild-type mice. in addition, plasmodium yoelii xl-17, a lethal strain, ... | 2014 | 24363183 |
| imaging plasmodium immunobiology in the liver, brain, and lung. | plasmodium falciparum malaria is responsible for the deaths of over half a million african children annually. until a decade ago, dynamic analysis of the malaria parasite was limited to in vitro systems with the typical limitations associated with 2d monocultures or entirely artificial surfaces. due to extremely low parasite densities, the liver was considered a black box in terms of plasmodium sporozoite invasion, liver stage development, and merozoite release into the blood. further, nothing w ... | 2014 | 24076429 |
| the evolution and diversity of a low complexity vaccine candidate, merozoite surface protein 9 (msp-9), in plasmodium vivax and closely related species. | the merozoite surface protein-9 (msp-9) has been considered a target for an anti-malarial vaccine since it is one of many proteins involved in the erythrocyte invasion, a critical step in the parasite life cycle. orthologs encoding this antigen have been found in all known species of plasmodium parasitic to primates. in order to characterize and investigate the extent and maintenance of msp-9 genetic diversity, we analyzed dna sequences of the following malaria parasite species: plasmodium falci ... | 2013 | 24044894 |
| plasmodium products contribute to severe malarial anemia by inhibiting erythropoietin-induced proliferation of erythroid precursors. | low reticulocytosis, indicating reduced red blood cell (rbc) output, is an important feature of severe malarial anemia. evidence supports a role for plasmodium products, especially hemozoin (hz), in suppressed erythropoiesis during malaria, but the mechanism(s) involved remains unclear. here, we demonstrated that low reticulocytosis and suppressed erythropoietin (epo)-induced erythropoiesis are features of malarial anemia in plasmodium yoelii- and plasmodium berghei anka-infected mice, similar t ... | 2014 | 23922378 |
| liver or blood-stage arrest during malaria sporozoite immunization: the later the better? | so far, the best immunization strategies to achieve high levels of protection against malaria are based on whole parasites. complete sterile protection can be obtained in rodent models after immunization with sporozoites and chemoprophylaxis, or with sporozoites attenuated either genetically or by radiation. these approaches target specific stages, with arrests occurring at different time-points of the parasite life cycle. here, we review these different approaches in relation to their capacity ... | 2013 | 23608185 |
| plasmodium liver load following parenteral sporozoite administration in rodents. | one of the bottlenecks in the development of a whole sporozoite malaria vaccine is the route and method of sporozoite administration. immunization and challenge of human volunteers by mosquito bites is effective, but cannot be used as a vaccine. intravenous immunization with sporozoites is effective in rodents and non-human primates, and being studied in humans, but is not yet used for licensed vaccines for infectious diseases. intradermal and subcutaneous immunization regimens show a strong dec ... | 2013 | 23063834 |
| endogenous galectin-3 controls experimental malaria in a species-specific manner. | galectins are evolutionarily conserved glycan-binding proteins with pleiotropic roles in innate and adaptive immune responses. galectin-3 has been implicated in several immunological processes as well as in pathogen recognition through specific binding to glycosylated receptors on the surface of host cells or microorganisms. in spite of considerable evidence supporting a role for galectin-3 in host-pathogen interactions, the relevance of this lectin in the regulation of the host defence mechanis ... | 2012 | 22486577 |
| extracellular atp triggers proteolysis and cytosolic ca²⁺ rise in plasmodium berghei and plasmodium yoelii malaria parasites. | plasmodium has a complex cell biology and it is essential to dissect the cell-signalling pathways underlying its survival within the host. | 2012 | 22420332 |
| the generation and evaluation of two panels of epitope-matched mouse igg1, igg2a, igg2b and igg3 antibodies specific for plasmodium falciparum and plasmodium yoelii merozoite surface protein 1-19 (msp1(19)). | murine immunoglobulin g (igg) plays an important role in mediating protective immune responses to malaria. we still know relatively little about which igg subclasses protect against this disease in mouse models, although igg2a and igg2b are considered to be the most potent and dominate in successful passive transfer experiments in rodent malarias. to explore the mechanism(s) by which the different mouse igg subclasses may mediate a protective effect, we generated mouse igg1, igg2a, igg2b and igg ... | 2012 | 22343045 |
| cloning, expression and functional characterization of heme detoxification protein (hdp) from the rodent malaria parasite plasmodium vinckei. | malaria parasite resides within the host red blood cells, where it degrades vast amount of haemoglobin. during haemoglobin degradation, toxic free heme is liberated which subsequently gets converted into hemozoin. this process is facilitated by action of various proteins viz. heme detoxification protein (hdp), and histidine rich proteins ii and iii (hrp ii & iii). out of these, hdp is the most potent in hemozoin formation and plays indispensible role for parasite survival. despite this, the deta ... | 2015 | 25891072 |
| crispr/cas9 mediated sequential editing of genes critical for ookinete motility in plasmodium yoelii. | crispr/cas9 has been successfully adapted for gene editing in malaria parasites including plasmodium falciparum and plasmodium yoelii. however, the reported methods were limited to editing one gene at a time. in practice, it is often desired to modify multiple genetic loci in a parasite genome. here we describe a crispr/cas9 mediated genome editing method that allows successive modification of more than one gene in the genome of p. yoelii using an improved single-vector system (pycm) we develope ... | 2017 | 28034675 |
| antimalarial activity of novel 4-aminoquinolines active against drug resistant strains. | in the present study we have synthesized a new class of 4-aminoquinolines and evaluated against plasmodium falciparum in vitro (3d7-sensitive strain & k1-resistant strain) and plasmodium yoelii in vivo (n-67 strain). among the series, eleven compounds (5, 6, 7, 8, 9, 11, 12, 13, 14, 15 and 21) showed superior antimalarial activity against k1 strain as compared to cq. in addition, all these analogues showed 100% suppression of parasitemia on day 4 in the in vivo mouse model against n-67 strain wh ... | 2017 | 27908538 |
| plasmosep: predicting surface-exposed proteins on the malaria parasite using semisupervised self-training and expert-annotated data. | accurate and comprehensive identification of surface-exposed proteins (seps) in parasites is a key step in developing novel subunit vaccines. however, the reliability of ms-based high-throughput methods for proteome-wide mapping of seps continues to be limited due to high rates of false positives (i.e., proteins mistakenly identified as surface exposed) as well as false negatives (i.e., seps not detected due to low expression or other technical limitations). we propose a framework called plasmos ... | 2016 | 27714937 |
| facilitation through altered resource availability in a mixed-species rodent malaria infection. | a major challenge in disease ecology is to understand how co-infecting parasite species interact. we manipulate in vivo resources and immunity to explain interactions between two rodent malaria parasites, plasmodium chabaudi and p. yoelii. these species have analogous resource-use strategies to the human parasites plasmodium falciparum and p. vivax: p. chabaudi and p. falciparum infect red blood cells (rbc) of all ages (rbc generalist); p. yoelii and p. vivax preferentially infect young rbcs (rb ... | 2016 | 27364562 |
| antimalarial activity of small-molecule benzothiazole hydrazones. | we synthesized a new series of conjugated hydrazones that were found to be active against malaria parasite in vitro, as well as in vivo in a murine model. these hydrazones concentration-dependently chelated free iron and offered antimalarial activity. upon screening of the synthesized hydrazones, compound 5f was found to be the most active iron chelator, as well as antiplasmodial. compound 5f also interacted with free heme (kd [equilibrium dissociation constant] = 1.17 ± 0.8 μm), an iron-contain ... | 2016 | 27139466 |
| marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by plasmodium. | the antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers ludwigothurea grisea and isostichopus badionotus, from the red alga botryocladia occidentalis, and from the marine sponge desmapsamma anchorata. in vitro experiments demonstrated for most compounds significant inhibiti ... | 2016 | 27071342 |
| isolation of invasive plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors. | malaria symptoms and pathogenesis are caused by blood stage parasite burdens of plasmodium spp., for which invasion of red blood cells (rbcs) by merozoites is essential. successful targeting by either drugs or vaccines directed against the whole merozoite or its antigens during its transient extracellular status would contribute to malaria control by impeding rbc invasion. to understand merozoite invasion biology and mechanisms, it is desired to obtain merozoites that retain their invasion activ ... | 2015 | 26684675 |
| characterization of plasmodium phosphatidylserine decarboxylase expressed in yeast and application for inhibitor screening. | phospholipid biosynthesis is critical for the development, differentiation and pathogenesis of several eukaryotic pathogens. genetic studies have validated the pathway for phosphatidylethanolamine synthesis from phosphatidylserine catalyzed by phosphatidylserine decarboxylase enzymes (psd) as a suitable target for development of antimicrobials; however no inhibitors of this class of enzymes have been discovered. we show that the plasmodium falciparum psd can restore the essential function of the ... | 2016 | 26585333 |
| immunogenicity and protective potential of a plasmodium spp. enolase peptide displayed on archaeal gas vesicle nanoparticles. | plasmodium falciparum enolase has been shown to localize on the surface of merozoites and ookinetes. immunization of mice with recombinant plasmodium enolase (rpfeno) showed partial protection against malaria. anti-rpfeno antibodies inhibited growth of the parasite in in vitro cultures and blocked ookinete invasion of mosquito midgut epithelium. it is hypothesized that parasite specific moonlighting functions (e.g. host cell invasion) may map on to unique structural elements of pfeno. since enol ... | 2015 | 26463341 |
| il-18-induced expression of high-affinity il-2r on murine nk cells is essential for nk-cell ifn-γ production during murine plasmodium yoelii infection. | early production of pro-inflammatory cytokines, including ifn-γ, is essential for control of blood-stage malaria infections. we have shown that ifn-γ production can be induced among human natural killer (nk) cells by coculture with plasmodium falciparum infected erythrocytes, but the importance of this response is unclear. to further explore the role of nk cells during malaria infection, we have characterized the nk-cell response of c57bl/6 mice during lethal (pyym) or nonlethal (py17xnl) p. yoe ... | 2015 | 26420375 |
| transient loss of protection afforded by a live attenuated non-typhoidal salmonella vaccine in mice co-infected with malaria. | in immunocompetent individuals, non-typhoidal salmonella serovars (nts) are associated with gastroenteritis, however, there is currently an epidemic of nts bloodstream infections in sub-saharan africa. plasmodium falciparum malaria is an important risk factor for invasive nts bloodstream in african children. here we investigated whether a live, attenuated salmonella vaccine could be protective in mice, in the setting of concurrent malaria. surprisingly, mice acutely infected with the nonlethal m ... | 2015 | 26366739 |
| in silico identification of genetically attenuated vaccine candidate genes for plasmodium liver stage. | genetically attenuated parasites (gaps) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. the genes targeted for deletion were often identified by trial and error. here we present a systematic gene - protein and transcript - expression analyses of several plasmodium species with the aim to identify candidate genes for the generation of n ... | 2015 | 26348884 |
| in vivo curative and protective potential of orally administered 5-aminolevulinic acid plus ferrous ion against malaria. | 5-aminolevulinic acid (ala) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ala is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. recent reports demonstrated that the combination of ala and ferrous ion (fe(2+)) inhibits the in vitro growth of the human malaria parasite plasmodium falciparum. to further explore the potential application of ala and ferrous ion as a ... | 2015 | 26324278 |
| discovery of new thienopyrimidinone derivatives displaying antimalarial properties toward both erythrocytic and hepatic stages of plasmodium. | a preliminary in vitro screening of compounds belonging to various chemical families from our library revealed the thieno[3,2-d]pyrimidin-4(3h)-one scaffold displayed a promising profile against plasmodium falciparum. then, 120 new derivatives were synthesized and evaluated in vitro; compared to drug references, 40 showed good activity toward chloroquine sensitive (ic50 35-344 nm) and resistant (ic50 45-800 nm) p. falciparum strains. they were neither cytotoxic (cc50 15-50 μm) toward hepg2 and c ... | 2015 | 25791675 |
| the rodent malaria lactate dehydrogenase assay provides a high throughput solution for in vivo vaccine studies. | rodent malaria is a useful model for evaluating the efficacy of malaria vaccine candidates; however, labor-intensive microscopic parasite counting hampers the use of an in vivo parasite challenge in high-throughput screening. the measurement of malaria parasite lactate dehydrogenase (pldh) activity, which is commonly used in the in vitro growth inhibition assay of plasmodium falciparum, may be the cheapest and simplest alternative to microscopic parasite counting. however, the pldh assay has not ... | 2015 | 25701649 |
| analogs of natural aminoacyl-trna synthetase inhibitors clear malaria in vivo. | malaria remains a major global health problem. emerging resistance to existing antimalarial drugs drives the search for new antimalarials, and protein translation is a promising pathway to target. here we explore the potential of the aminoacyl-trna synthetase (ars) family as a source of antimalarial drug targets. first, a battery of known and novel ars inhibitors was tested against plasmodium falciparum cultures, and their activities were compared. borrelidin, a natural inhibitor of threonyl-trn ... | 2014 | 25489076 |
| humoral immune responses to a recombinant plasmodium vivax tryptophan-rich antigen among plasmodium vivax-infected patients and its localization in the parasite. | our recent studies have focused on the identification and characterization of the tryptophan-rich proteins of the plasmodium vivax parasite where their role in the elicitation of humoral and cellular responses and erythrocyte-binding activity was investigated. here, we report the humoral responses of a 32.4-kda p. vivax tryptophan-rich antigen (pvtrag32.4) among the sera of p. vivax-infected patients. pvtrag32.4 also contains an unusually high percentage of tryptophan residues (10.7 %) that are ... | 2015 | 25467946 |
| a comprehensive evaluation of rodent malaria parasite genomes and gene expression. | rodent malaria parasites (rmp) are used extensively as models of human malaria. draft rmp genomes have been published for plasmodium yoelii, p. berghei anka (pba) and p. chabaudi as (pcas). although availability of these genomes made a significant impact on recent malaria research, these genomes were highly fragmented and were annotated with little manual curation. the fragmented nature of the genomes has hampered genome wide analysis of plasmodium gene regulation and function. | 2014 | 25359557 |
| plasmodium falciparum, but not p. vivax, can induce erythrocytic apoptosis. | apoptosis can occur in red blood cells (rbc) and seems to be involved in hematologic disorders related to many diseases. in malaria it is known that parasitized rbc (prbc) is involved in the development of anemia and thrombosis; however, non-parasitized rbc (nrbc) apoptosis could amplify these malaria-associated hematologic events. in fact, in experimental malaria, increased levels of apoptosis were observed in nrbc during lethal plasmodium yoelii 17xl infection, but in human malaria erythrocyti ... | 2014 | 25325923 |
| synthesis of chiral chloroquine and its analogues as antimalarial agents. | in this investigation, we describe a new approach to chiral synthesis of chloroquine and its analogues. all tested compounds displayed potent activity against chloroquine sensitive as well as chloroquine resistant strains of plasmodium falciparum in vitro and plasmodium yoelii in vivo. compounds s-13 b, s-13c, s-13 d and s-13 i displayed excellent in vitro antimalarial activity with an ic50 value of 56.82, 60.41, 21.82 and 7.94 nm, respectively, in the case of resistant strain. furthermore, comp ... | 2014 | 25284252 |
| immunization with a functional protein complex required for erythrocyte invasion protects against lethal malaria. | an essential step in the invasion of red blood cells (rbcs) by plasmodium falciparum (pf) merozoites is the binding of rhoptry neck protein 2 (ron2) to the hydrophobic groove of apical membrane antigen 1 (ama1), triggering junction formation between the apical end of the merozoite and the rbc surface to initiate invasion. vaccination with ama1 provided protection against homologous parasites in one of two phase 2 clinical trials; however, despite its ability to induce high-titer invasion-blockin ... | 2014 | 24958881 |
| amphiphilic dendritic derivatives as nanocarriers for the targeted delivery of antimalarial drugs. | it can be foreseen that in a future scenario of malaria eradication, a varied armamentarium will be required, including strategies for the targeted administration of antimalarial compounds. the development of nanovectors capable of encapsulating drugs and of delivering them to plasmodium-infected cells with high specificity and efficacy and at an affordable cost is of particular interest. with this objective, dendritic derivatives based on 2,2-bis(hydroxymethyl)propionic acid (bis-mpa) and pluro ... | 2014 | 24930847 |
| cd81 is required for rhoptry discharge during host cell invasion by plasmodium yoelii sporozoites. | plasmodium sporozoites are transmitted by anopheles mosquitoes and first infect the liver of their mammalian host, where they develop as liver stages before the onset of erythrocytic infection and malaria symptoms. sporozoite entry into hepatocytes is an attractive target for anti-malarial prophylactic strategies but remains poorly understood at the molecular level. apicomplexan parasites invade host cells by forming a parasitophorous vacuole that is essential for parasite development, a process ... | 2014 | 24798694 |
| use of poly(amidoamine) drug conjugates for the delivery of antimalarials to plasmodium. | current malaria therapeutics demands strategies able to selectively deliver drugs to plasmodium-infected red blood cells (prbcs) in order to limit the appearance of parasite resistance. here, the poly(amidoamines) agma1 and isa23 have been explored for the delivery of antimalarial drugs to prbcs. agma1 has antimalarial activity per se as shown by its inhibition of the in vitro growth of plasmodium falciparum, with an ic₅₀ of 13.7 μm. fluorescence-assisted cell sorting data and confocal fluoresce ... | 2014 | 24412735 |
| synthesis and bioevaluation of novel 4-aminoquinoline-tetrazole derivatives as potent antimalarial agents. | a series of novel tetrazole derivatives of 4-aminoquinoline were synthesized and screened for their antimalarial activities against both chloroquine-senstive (3d7) and chloroquine-resistant (k1) strains of plasmodium falciparum as well as for cytotoxicity against vero cell lines. most of the synthesized compounds exhibited potent antimalarial activity as compared to chloroquine against k1-strain. compounds with significant in vitro antimalarial activity were then evaluated for their in vivo effi ... | 2013 | 23792317 |
| ketoconazole, a cytochrome p(450) inhibitor can potentiate the antimalarial action of α/β arteether against mdr plasmodium yoelii nigeriensis. | the emergence of multidrug resistant (mdr) strains of plasmodium falciparum in south east asia and other tropical countries, is posing serious challenge for the international efforts to eradicate malaria. new drug target/act/non-act combinations need to be discovered to control the spread of mdr malaria. the present communication deals with antimalarial potential of a new combination comprising of ketoconazole (ktz) (an antifungal/inhibitor of cyp3a4) and artemisinin derivative α/β arteether (ar ... | 2013 | 23391499 |
| multivariable analysis of host amino acids in plasma and liver during infection of malaria parasite plasmodium yoelii. | malaria is the most significant human parasitic disease, and yet understanding of the energy metabolism of the principle pathogen, plasmodium falciparum, remains to be fully elucidated. amino acids were shown to be essential nutritional requirements since early times and much of the current knowledge of plasmodium energy metabolism is based on early biochemical work, performed using basic analytical techniques, carried out almost exclusively on human plasma with considerable inter-individual var ... | 2013 | 23324562 |
| inactivation of plasmodium spp. in plasma and platelet concentrates using riboflavin and ultraviolet light. | photochemical treatment of blood products could help prevent transfusion-transmitted malaria and reduce the need for donor deferrals. in this study we evaluated the effectiveness of riboflavin and ultraviolet (uv) light against both plasmodium falciparum, which causes the most severe form of human malaria, and plasmodium yoelii, an in vivo murine model for malaria. | 2013 | 23320495 |
| blackwater fever like in murine malaria. | blackwater fever (bwf) is the term used to designate the occurrence of hemoglobin pigments in the urine of patients infected with malaria parasites. bwf is more often associated with plasmodium falciparum infection in man. the pathogenesis of bwf has not been explained satisfactorily. in the present study, the clinical and pathological observations made upon cd1 mice infected with plasmodium yoelii yoelii lethal strain with clinical signs of hemoglobinuria and acute renal failure were evaluated. ... | 2013 | 23254588 |
| time-lapse imaging of red blood cell invasion by the rodent malaria parasite plasmodium yoelii. | in order to propagate within the mammalian host, malaria parasites must invade red blood cells (rbcs). this process offers a window of opportunity in which to target the parasite with drugs or vaccines. however, most of the studies relating to rbc invasion have analyzed the molecular interactions of parasite proteins with host cells under static conditions, and the dynamics of these interactions remain largely unstudied. time-lapse imaging of rbc invasion is a powerful technique to investigate c ... | 2012 | 23227208 |