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PubMed2000

Description of Madathamugadia hiepei n. sp. (nematoda: Splendidofilariinae), a parasite of a South African gecko, and its development in laboratory bred Phlebotomus dubosqi (Diptera: Psychodidae).

Madathamugadia hiepei n. sp., Splendidofilariinae, a parasite of a South African gecko Pachydactylus turneri is described together with its development obtained experimentally in Phlebotomus duboscqi (Diptera: Psychodidae: Phlebotominae). This new species differs from the two small, more highly evolved groups with a short tail and atrophied postcloacal papillae, the first group consisting of two Madagascan species, M. zonosauri and M. hopluri, parasites of the Gerrhosauridae and Iguanidae, and the second containing three species from the Ethiopian Region, M. huambensis, M. versterae and M. bissani, parasites of the Scincidae. It also differs from M. ineichi, the most primitive species of the genus (cuticularised buccal capsule, no atrophy of head papillae and largest number of precloacal papillae), a parasite of the Cordylidae in South Africa. M. hiepei is close to the two species parasitic in the Gekkonidae of the Mediterranean subregion, M. ivaschkini and M. wanjii, all three of which have a post-oesophageal vulva. However, the new species can be distinguished from the Mediterranean parasites by (a) the shorter oesophagus, (b) the number and position of the cloacal papillae and (c) the microfilaria. The three filariae of this group and M. ineichi, the only ones of which aspects of the life-cycles are known, experimentally develop in phlebotomine sand flies.

Animals↗
PubMed2000

Effects of parasitism and pesticide exposure on characteristics and functions of hemocyte populations in the freshwater snail Lymnaea palustris (Gastropoda, Pulmonata).

Morphological characteristics and functions of hemocytes were used to compare the immunological effects of biological and chemical stress in the freshwater snail Lymnaea palustris. Animals were either infected by a trematode parasite (Metaleptocephalus sp.), or exposed to environmental contaminants, namely atrazine and hexachlorobenzene (HCB). Three populations of circulating hemocytes, morphologically and cytochemically distinct (round cells, hyalinocytes, granulocytes), were identified in both control and parasitized or pesticide-exposed snails. After 6 h of exposure, HCB and atrazine resulted in 8-fold increases in the mean total number of hemocytes, whereas only a 2.2-fold increase was observed 6 h after cercaria emission in parasitized snails. The impact of HCB was limited to the first 24 h of exposure, whereas long-lasting effects of atrazine were observed. Hyalinocytes and, to a lesser extent, round cells contributed most to the increases in hemocyte density in pesticide-exposed snails. Parasitism and atrazine treatment resulted in significant increases of lectin-stained hemocytes, whereas exposure to HCB did not affect the percentages of stained and unstained cells. Hemocyte phagocytic activity increased in HCB-exposed snails but with no concomitant change of the oxidative burst. Opposite results were obtained in atrazine-treated snail hemocytes, with unchanged phagocytosis and decreased phorbol 12-myristate 13-acetate-stimulated production of reactive oxygen intermediates. No increase in phagocytosis, or in the production of reactive oxygen intermediates, was observed in hemocytes from parasitized snails. Infection with the immunologically compatible trematode parasite Metaleptocephalus sp. and exposure to atrazine generated similar reactions from circulating hemocytes, whereas a different response pattern was observed in HCB-exposed snails.

Animals↗
PubMed2003

Investigations on the influence of helminth parasites on vaccination of chickens against Newcastle disease virus under village conditions.

Prevalence studies have shown that almost 100% of free-range chickens are infected with a wide range of parasites. The infections are mostly subclinical in nature, resulting in production losses and occasionally mortality. Newcastle disease (ND) on the other hand, results in high mortality rates during epidemics. ND is a limiting factor for increasing poultry production in many tropical countries, where frequent reports indicate vaccination failures. The aim of our study was to investigate the influence of helminths on the antibody response after vaccination against Newcastle disease of free-range chickens naturally infected with parasites. Sixty chickens were divided into six groups, of which three were vaccinated against ND with a live De Soto vaccine, while the other three remained non-vaccinated. One group within the vaccinated groups and the one within the non-vaccinated group was kept naturally infected with helminth parasites, while the other two groups in each set were dewormed with fenbendazole and niclosamide, and one of each of these groups was subsequently infected with Ascaridia galli. After vaccination, all the groups were followed for 5 weeks and their antibody titres were determined weekly using a HI test. All the birds were finally challenged 4 weeks after vaccination with a virulent velogenic ND virus obtained from a field outbreak. All the vaccinated chickens seroconverted and had high antibody levels after 3 weeks, but these dropped to low levels at 4 weeks after vaccination. After challenge, the antibody titres rose in the dewormed groups but not in the parasite-infected groups. After 5 weeks, all the parasite-infected animals had significantly lower antibody titres than the dewormed animals. All the vaccinated chickens survived the challenge infection, emphasizing the importance of the cellular immune response. Further studies are needed to examine the effects of the parasitic infection on protection against ND over a longer period.

Analysis of Variance↗
PubMedDate not supplied

Malaria parasites--discovery of the early liver form.

Infections of mammalian malaria parasites start when sporozoites from an infected anopheline mosquito are injected into the bloodstream of the host. The sporozoites enter the hepatocytes and become transformed into exoerythrocytic schizonts. Since the discovery of the primate parasite Plasmodium cynomolgi in monkey hepatocytes and the rodent parasite Plasmodium berghei in hamster hepatocytes, the ultrastructure of these stages has been extensively studied both in primate and rodent plasmodia. These observations relate only to the development of the exoerythrocytic schizont 25 h after sporozoite injection until the final maturation (of P. berghei) 50 h post-inoculation. Recently, we have studied the route of entry of sporozoites across the cellular lining of liver sinusoids and invasion of the liver parenchymal cells by using transmission electron microscopy. The results of these studies in combination with other physiological experiments strongly suggested that the sporozoite was initially harboured by the Kupffer cell, from which the parasite escaped into the neighbouring hepatocyte. The migration of sporozoites from liver sinusoids to hepatocytes can be achieved within a few minutes. We present here the first ultrastructural observations on the natural transformation of intrahepatocytic sporozoites into exoerythrocytic forms in vivo, using the rodent malaria parasite P. berghei in a laboratory host, the Brown Norway rat. These observations complete the search for the final link in the life cycle of malaria parasites.

Animals↗
PubMed2006

Parasitic infections in transplant recipients.

Parasitic infections are important complications of organ transplantation that are often overlooked in the differential diagnosis of post-transplantation pyrexial illness. Although their frequency is unknown, they seem to be much less prevalent than bacterial and viral infections. Only 5% of human pathogenic parasites have been reported to cause significant illness in transplant recipients. Infection can occur via transmission with the graft or blood transfusion, or be acquired de novo from the environment. Recrudescence of dormant infection can lead to active disease. Post-transplantation parasitic disorders tend to cluster into two clinical profiles. First, an acute systemic illness with anemia, constitutional manifestations and variable stigmata of organ involvement; acute graft dysfunction can lead to confusion and acute rejection. Protozoa including malarial Plasmodium, Leishmania, Trypanosoma and Toxoplasma are associated with this profile. The second typical manifestation encompasses a few localized syndromes, usually associated with the lower gastrointestinal tract, caused by either protozoa (Cryptosporidium and microsporidia) or nematodes (Strongyloides and Ascaris). Dissemination of localized infections can lead to life-threatening systemic manifestations. A high index of suspicion is essential, as diagnosis requires special sampling techniques and laboratory procedures. Definitive diagnosis is usually achieved by detecting the parasite in the patient's tissues or body fluids by histological examination or culture, or by polymerase chain reaction amplification of the parasite-specific antigen sequence. Antibody detection using serological techniques is also possible in a few parasitic infections. Certain lesions have characteristic radiological appearances, hence the value of imaging, particularly in the cerebral syndromes. Treatment is usually straightforward (broad spectrum or specific drugs), yet some species are drug resistant.

Animals↗
PubMed1999

Host and parasite population structure in a natural plant-pathogen system

We investigated the genetic population structure in a metapopulation of the plant Silene latifolia (Caryophyllaceae) and its fungal pathogen Microbotryum violaceum (Ustilaginales), a pollinator-borne disease. Population structure of the host plant was estimated using allozyme markers and that of the fungus by microsatellites. Both host and parasite showed significant differentiation, but parasite populations were 12 times more strongly differentiated than those of the hosts. We found significant isolation by distance for host populations but not for parasite populations. Higher population differentiation for the parasite may result from small effective population size, high selfing rates, or low migration rate. In this system, hosts are obligate outcrossers and they migrate by seeds and pollen, whereas parasites can self-fertilize and migrate only on pollinating insects. We discuss the effect of limited gene flow in this parasite on its coevolutionary interaction with its host, and its potential for local adaptation on sympatric host populations.

Journal Article↗
PubMed1987

An intracellular simian malarial parasite (Plasmodium knowlesi) induces stage-dependent alterations in membrane phospholipid organization of its host erythrocyte.

The membrane phospholipid organization in monkey erythrocytes harbouring different developmental stages of the simian malarial parasite Plasmodium knowlesi was studied using phospholipase A2 from two different sources and Merocyanine 540 as the external-membrane probes. Experiments were done to confirm that the phospholipases did not penetrate into the infected cells or hydrolyse phospholipids during membrane isolation. The parasite-free erythrocyte membrane was isolated by differential centrifugation or by using the cationic beads Affi-Gel 731. The purity of the membranes was established by optical and electron microscopy, and by assaying the parasite-specific enzyme glutamate dehydrogenase. About 10% of the phosphatidylethanolamine and none of phosphatidylserine were hydrolysed by the phospholipases in intact normal monkey erythrocytes. However, accessibility of these aminophospholipids to the enzymes was significantly enhanced in the infected cells under identical conditions. The degree of this enhancement depended on the developmental stage of the intracellular parasite, but not on the parasitaemia levels in the infected monkeys, and increased with the parasite growth inside the cells. Analogously, Merocyanine 540 was found to label the trophozoite- or schizont-infected erythrocytes, but not the ring-infected or normal cells. These results demonstrate that the intracellular malarial parasite produces stage-dependent alterations in the membrane phospholipid organization of its host erythrocyte.

Animals↗
PubMed1998

Increased choline transport in erythrocytes from mice infected with the malaria parasite Plasmodium vinckei vinckei.

Parasitized erythrocytes from mice infected with the murine malaria parasite Plasmodium vinckei vinckei showed a marked increase in the rate of influx of choline compared with erythrocytes from uninfected mice. In contrast, uninfected erythrocytes from P. vinckei-infected animals transported choline at the same rate as those from uninfected mice. The increased influx of choline into parasitized cells was via two discrete routes. One was a saturable pathway with a Km similar to that of the choline carrier of normal erythrocytes but a Vmax approx. 20-fold higher than that observed in uninfected cells. The other was a non-saturable pathway inhibited by furosemide. At choline concentrations within the normal physiological plasma concentration range, the former pathway contributed approx. two-thirds and the latter approx. one-third of the influx of choline into parasitized cells. The characteristics of the furosemide-sensitive pathway were similar to those of a broad-specificity pathway that is induced in human erythrocytes infected in vitro with Plasmodium falciparum. The results of this study rule out the possibility that the induced transport pathway of P. falciparum-infected erythrocytes is an artifact arising in vitro from the long-term culture of parasitized cells and provide evidence that this pathway makes a significant contribution to the uptake of choline into the parasitized cells of malaria-infected animals.

Animals↗
PubMed2001

Growth of Plasmodium falciparum induces stage-dependent haemichrome formation, oxidative aggregation of band 3, membrane deposition of complement and antibodies, and phagocytosis of parasitized erythrocytes.

Plasmodium falciparum-parasitized erythrocytes (RBCs) are progressively transformed into non-self cells, phagocytosed by human monocytes. Haemichromes, aggregated band 3 (Bd3) and membrane-bound complement fragment C3c and IgG were assayed in serum-opsonized stage-separated parasitized RBCs. All parameters progressed from control to rings to trophozoites to schizonts: haemichromes, nil; 0.64 +/- 0.12; 5.6 +/- 1.91; 8.4 +/- 2.8 (nmol/ml membrane); Bd3, 1 +/- 0.1; 4.3 +/- 1.5; 23 +/- 5; 25 +/- 6 (percentage aggregated); C3c, 31 +/- 11; 223 +/- 86; 446 +/- 157; 620 +/- 120 (mOD405/min/ml membrane); IgG, 35 +/- 12; 65 +/- 23; 436 +/- 127; 590 +/- 196 (mOD405/min/ml membrane). All increments in rings versus controls and in trophozoites versus rings were highly significant. Parasite development in the presence of 100 micromol/l beta-mercaptoethanol largely reverted haemichrome formation, Bd3 aggregation, C3c and IgG deposition and phagocytosis. Membrane proteins extracted by detergent C12E8 were separated on Sepharose CL-6B. Haemichromes, C3c and IgG were present exclusively in the high-molecular-weight fractions together with approximately 30% of Bd3, indicating the oxidative formation of immunogenic Bd3 aggregates. Immunoblots of separated membrane proteins with anti-Bd3 antibodies confirmed Bd3 aggregates that, in part, did not enter the gel. Immunoprecipitated antibodies eluted from trophozoites reacted preferentially with aggregated Bd3. Changes in parasitized RBC membranes and induction of phagocytosis were similar to oxidatively damaged, senescent or thalassaemic RBC, indicating that parasite-induced oxidative modifications of Bd3 were per se sufficient to induce and enhance phagocytosis of malaria-parasitized RBC.

Animals↗
PubMed1996

The isolation and characterization of genomic and cDNA clones coding for a cdc2-related kinase (ThCRK2) from the bovine protozoan parasite Theileria.

The tick-transmitted protozoan parasites Theileria annulata and Theileria parva are important intracellular pathogens of domestic cattle in tropical and subtropical regions. Proliferative phases take place within both lymphocytes and erythrocytes. The lymphocyte is stimulated to enter the cell cycle by the parasite and the multinucleate parasite can establish a state in which karyokinesis and cytokinesis occur in phase with the host cell. The link between parasite nuclear division and cytokinesis is altered during the formation of merozoites (a non-dividing, invasive, extracellular stage). These features imply a high degree of control over parasite nuclear division and cytokinesis. Two different approaches have been used to identify clones from both species which are extremely highly conserved homologues. These encode a cdc2-related kinase which is > 60% identical to eukaryotic cyclin-dependent kinases of the p34cdc2/p32CDK2 subfamily. There is typical conservation of kinase domains, implying an in vivo protein kinase activity for the polypeptide. The PSTAIRE region, implicated in cyclin binding, is well conserved suggesting that ThCRK2 will bind cyclin molecules closely related to the eukaryotic A/B-type cyclins. However, there is divergence in certain key motifs potentially associated with binding of molecules that regulate the activity of the kinase. Expression patterns of RNA and protein indicate that ThCRK2 is likely to function in all dividing stages of the parasite and, taken together, the results point to a central role in the regulation of nuclear division.

Amino Acid Sequence↗
PubMed2002

A malaria scavenger receptor-like protein essential for parasite development.

Malaria parasites suffer severe losses in the mosquito as they cross the midgut, haemolymph and salivary gland tissues, in part caused by immune responses of the insect. The parasite compensates for these losses by multiplying during the oocyst stage to form the infectious sporozoites. Upon human infection, malaria parasites are again attenuated by sustained immune attack. Here, we report a single copy gene that is highly conserved amongst Plasmodium species that encodes a secreted protein named PxSR. The predicted protein is composed of a unique combination of metazoan protein domains that have been previously associated with immune recognition/activation and lipid/protein adhesion interactions at the cell surface, namely: (i) scavenger receptor cysteine rich (SRCR); (ii) pentraxin (PTX); (iii) polycystine-1, lipoxygenase, alpha toxin (LH2/PLAT); (iv) Limulus clotting factor C, Coch-5b2 and Lgl1 (LCCL). In our assessment the PxSR molecule is completely novel in biology and is only found in Apicomplexa parasites. We show that PxSR is expressed in sporozoites of both human and rodent malaria species. Disruption of the PbSR gene in the rodent malaria parasite P. berghei results in parasites that form normal numbers of oocysts, but fail to produce any sporozoites. We suggest that, in addition to a role in sporogonic development, PxSR may have a multiplicity of functions.

Amino Acid Sequence↗
PubMed2002

Arginase I induction in macrophages, triggered by Th2-type cytokines, supports the growth of intracellular Leishmania parasites.

Leishmania spp. are intracellular protozoan parasites that invade and replicate within macrophages. In a previous report, we have demonstrated that the growth of intracellular amastigotes could be controlled by inhibition of arginase. This enzyme, induced in host cells by Th2 cytokines, synthesizes L-ornithine which can be used by parasites to generate polyamines and proliferate. In this study, we have designed experiments to better analyse the dependence of parasite proliferation on arginase induction in infected macrophages. Treatment of Leishmania major-infected BALB/c macrophages with interleukin (IL)-4, IL-10 or transforming growth factor-beta, which are all inducers of arginase I in murine macrophages, led to a proportional increase in the number of intracellular amastigotes. Moreover, parasite proliferation and arginase activity levels in macrophages from the susceptible BALB/c mice were significantly higher than those from infected C57BL/6 cells when treated with identical doses of these cytokines, indicating that a strong correlation exist between the permissibility of host cells to L. major infection and the induction of arginase I in macrophages. Specific inhibition of arginase by N(omega)-hydroxy-nor-L-arginine (nor-LOHA) reverted growth, while L-ornithine and putrescine promoted parasite proliferation, indicating that the parasite cell division depends critically on the level of L-ornithine available in the host. Therefore, arginase induction in the context of a Th2 predominant response might be a contributor to susceptibility in leishmaniasis.

Animals↗
PubMed1999

NRSA-1: a resistance gene homolog expressed in roots of non-host plants following parasitism by Striga asiatica (witchweed).

Studies of the initial interactions of Striga asiatica with the non-host plant species Tagetes erecta (marigold) established that parasite penetration through the root is arrested most frequently in the cortex. The arrest of parasite ingress is associated with browning and necrosis of root cortical cells flanking the invading endophyte and with increased intracellular wall appositions on the root cell walls directly adjacent to the plant-parasite interface. Using a polymerase chain reaction-based differential cDNA amplification strategy followed by 5'-RACE, we have identified several gene products whose expression is induced in marigold roots during attempted parasitism by Striga. Among these was a 917 bp cDNA encoding a 221 amino acid protein with significant homology to proteins encoded by disease resistance genes from other plant species, including N, RPP5, L6 and M. This cDNA was subsequently used to isolate a nuclear gene, designated NRSA-1, for non-host resistance to Striga asiatica. NRSA-1 is a member of a small gene family in marigold consisting of two to four members. RNA gel blot analysis showed that NRSA-1 transcripts accumulate to high levels in roots near the site of Striga invasion within 120 h after parasite attachment, and appear at lower levels throughout the rest of the plant under Striga parasitism. NRSA-1 expression is rapidly induced by treatment with jasmonic acid (JA), but not by mechanical wounding, treatment with salicylic acid, paraquat or ABA. A possible role for NRSA-1 in the non-host resistance mechanism is discussed.

Amino Acid Sequence↗
PubMed2001

Fluorescent Plasmodium berghei sporozoites and pre-erythrocytic stages: a new tool to study mosquito and mammalian host interactions with malaria parasites.

To track malaria parasites for biological studies within the mosquito and mammalian hosts, we constructed a stably transformed clonal line of Plasmodium berghei, PbFluspo, in which sporogonic and pre-erythrocytic liver-stage parasites are autonomously fluorescent. A cassette containing the structural gene for the FACS-adapted green fluorescent protein mutant 2 (GFPmut2), expressed from the 5' and 3' flanking sequences of the circumsporozoite (CS) protein gene, was integrated and expressed at the endogenous CS locus. Recombinant parasites, which bear a wild-type copy of CS, generated highly fluorescent oocysts and sporozoites that invaded mosquito salivary glands and were transmitted normally to rodent hosts. The parasites infected cultured hepatocytes in vitro, where they developed into fluorescent pre-erythrocytic forms. Mammalian cells infected by these parasites can be separated from non-infected cells by fluorescence activated cell sorter (FACS) analysis. These fluorescent insect and mammalian stages of P. berghei should be useful for phenotypic studies in their respective hosts, as well as for identification of new genes expressed in these parasite stages.

Animals↗
PubMed1987

Fractionation of mouse malarious blood according to parasite developmental stage, using a Percoll-sorbitol gradient.

Asexual intraerythrocytic malarial parasites permeabilize the membrane of their host cell to small monelectrolytes and anions. Since permeabilization increases with parasite maturation, this property has been used previously to fractionate blood infected with Plasmodium falciparum and P. knowlesi according to the developmental stage of the parasite, using Percoll-sorbitol density gradients. We have extended this method to fractionate mouse blood infected with four species of rodent malaria: P. chahaudi, P. vinckei, P. voelii and P. berghei. While the method works in principle in this case, the polyparasitism which characterizes these species prevented explicit separation according to developmental stage. Hence, erythrocytes harbouring several ring-stage parasites appeared in the same fraction which contained cells hosting a single trophozoite, and polyparasitized trophozoites were associated with singly-infected schizont. This observation implies that permeabilization of the host cell membrane results from the integrated metabolic activity of the parasite(s) and is not related to a specific phase of parasite development.

Animals↗
PubMed1997

Ultrastructural changes in parasites induced by nanoparticle-bound pentamidine in a Leishmania major/mouse model.

Drug targeting enhances drug efficacy. This principle was tested in the treatment of an experimental visceral leishmaniasis. Using transmission electron microscopy (TEM) we localized pentamidine-loaded polymethocrylate nanoparticles in the liver of mice infected with Leishmania major and compared the ultrastructural changes in the parasites of these mice when they were treated with bound versus free pentamidine. Between days 13 and 17 after infection, loaded nanoparticles treated group were injected i.v. with 3 doses of 0.17 mg/kg bound pentamidine loaded on 2 x 10(11) nanospheres; control groups received 2 x 10(11) unloaded nanospheres. Drug reference control groups received five doses of 200 mg/kg pentavalent antimony (Glucantime) or three doses of free pentamidine (0.17 mg/kg or 2.28 mg/kg). Mice treated with bound pentamidine displayed a 77% reduction in their parasite burden versus the untreated controls. Nanoparticles were located by TEM inside parasitized Küpffer cells, in the phagolysosomes without entering the Leishmania. The low dose of 0.17 mg/kg bound pentamidine damaged the Leishmania to the same extent as 2.28 mg/kg of free pentamidine (the usual dose in human chemotherapy). In the parasites inside the Küpffer cells, TEM showed a swollen mitochondrian with loss of cristae, destruction or fragmentation of the kinetoplast, loss of ribosomes and destruction of parasite structures except for the subpellicular microtubules. This study therefore shows that a dose of bound pentamidine 13 times smaller than the usual dose of free pentamidine has a similar effect on the parasite.

Animals↗
PubMed2004

Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites.

Among potential new targets for antimalarial chemotherapy are Plasmodium falciparum cysteine proteases, known as falcipains. Falcipain-2 and falcipain-3 are food vacuole hemoglobinases that may have additional functions. The function of falcipain-1 remains uncertain. To better characterize the role of falcipain-1 in erythrocytic parasites, we disrupted the falcipain-1 gene and characterized recombinant parasites. Disruption of the falcipain-1 gene was confirmed with Southern blots, and loss of expression of falcipain-1 was confirmed with immunoblots and by loss of labeling with a specific protease inhibitor. Compared with wild-type parasites, falcipain-1 knockout parasites developed normally, with the same morphology, multiplication rate, and invasion efficiency, and without significant differences in sensitivity to cysteine protease inhibitors. In wild-type and knockout parasites, cysteine protease inhibitors blocked hemoglobin hydrolysis in trophozoites, with a subsequent block in rupture of erythrocytes by mature schizonts, but they did not inhibit erythrocyte invasion by merozoites. Our results indicate that although falcipain-1 is expressed by erythrocytic parasites, it is not essential for normal development during this stage or for erythrocyte invasion.

Animals↗
PubMed2006

The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum.

The human malaria parasite Plasmodium falciparum relies on the acquisition of host purines for its survival within human erythrocytes. Purine salvage by the parasite requires specialized transporters at the parasite plasma membrane (PPM), but the exact mechanism of purine entry into the infected erythrocyte, and the primary purine source used by the parasite, remain unknown. Here, we report that transgenic parasites lacking the PPM transporter PfNT1 (P. falciparum nucleoside transporter 1) are auxotrophic for hypoxanthine, inosine, and adenosine under physiological conditions and are viable only if these normally essential nutrients are provided at excess concentrations. Transport measurements across the PPM revealed a severe reduction in hypoxanthine uptake in the knockout, whereas adenosine and inosine transport were only partially affected. These data provide compelling evidence for a sequential pathway for exogenous purine conversion into hypoxanthine using host enzymes followed by PfNT1-mediated transport into the parasite. The phenotype of the conditionally lethal mutant establishes PfNT1 as a critical component of purine salvage in P. falciparum and validates PfNT1 as a potential therapeutic target.

Animals↗