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At least 19 recordsLinked to original sources
PubMed2025

Biomathematical enzyme kinetics model of prebiotic autocatalytic RNA networks: degenerating parasite-specific hyperparasite catalysts confer parasite resistance and herald the birth of molecular immunity.

Catalysis and specifically autocatalysis are the quintessential building blocks of life. Yet, although autocatalytic networks are necessary, they are not sufficient for the emergence of life-like properties, such as replication and adaptation. The ultimate and potentially fatal threat faced by molecular replicators is parasitism; if the polymerase error rate exceeds a critical threshold, even the fittest molecular species will disappear. Here we have developed an autocatalytic RNA early life mathematical network model based on enzyme kinetics, specifically the steady-state approximation. We confirm previous models showing that these second-order autocatalytic cycles are sustainable, provided there is a sufficient nucleotide pool. However, molecular parasites become untenable unless they sequentially degenerate to hyperparasites (i.e. parasites of parasites). Parasite resistance-a parasite-specific host response decreasing parasite fitness-is acquired gradually, and eventually involves an increased binding affinity of hyperparasites for parasites. Our model is supported at three levels; firstly, ribozyme polymerases display Michaelis-Menten saturation kinetics and comply with the steady-state approximation. Secondly, ribozyme polymerases are capable of sustainable auto-amplification and of surmounting the fatal error threshold. Thirdly, with growing sequence divergence of host and parasite catalysts, the probability of self-binding is expected to increase and the trend towards cross-reactivity to diminish. Our model predicts that primordial host-RNA populations evolved via an arms race towards a host-parasite-hyperparasite catalyst trio that conferred parasite resistance within an RNA replicator niche. While molecular parasites have traditionally been viewed as a nuisance, our model argues for their integration into the host habitat rather than their separation. It adds another mechanism-with biochemical precision-by which parasitism can be tamed and offers an attractive explanation for the universal coexistence of catalyst trios within prokaryotes and the virosphere, heralding the birth of a primitive molecular immunity.

Kinetics↗
PubMed1992

The mortality and fecundity of Haemonchus contortus in parasite-naive and parasite-exposed sheep following single experimental infections.

Parasite-exposed lambs and their parasite-naive controls were experimentally infected once only with 30,000 H. contortus larvae at 3, 9, 12, and 20 weeks following termination of a moderate immunizing infection of 30,000 H. contortus larvae. Previously exposed lambs, challenged at 3 weeks, had a significant reduction in the total H. contortus worm burden as compared to parasite-naive controls. No difference in the total H. contortus worm burden was found between parasite-exposed or parasite-naive lambs challenged at 9 weeks or thereafter. Female worms were found to be significantly smaller in lambs previously exposed to the parasite as compared to those found in parasite-naive lambs. The average parasite fecundity was 4700 eggs per female worm per day. Previous exposure of the lambs to the parasite had no effect on parasite fecundity. Various mathematical models were used to examine parasite fecundity. Parasite fecundity was found to increase in the initial post-challenge period reaching a constant value approximately 58 days after challenge infection. No density-dependent constraints on fecundity were observed.

Animals↗
PubMed1987

Use of an oxfendazole pulse release bolus in the control of parasitic gastroenteritis and parasitic bronchitis in first-season grazing calves.

The efficacy of the oxfendazole pulse release bolus system for the control of parasitic gastroenteritis and parasitic bronchitis in first-season grazing calves was evaluated in Belgium. Twenty-two calves were allocated to two groups. The calves in one group received a bolus at the time of turn out, while the other group remained untreated. The efficacy of the bolus was assessed by comparison of faecal worm egg counts, plasma pepsinogen concentrations, the antibody response to Ostertagia, Cooperia and Dictyocaulus species total plasma protein and albumin concentrations, and weight gains throughout the grazing season and the housing period. The oxfendazole pulse release bolus provided good control of parasitic gastroenteritis dominated by ostertagia. The effects of parasitic gastritis were greatly reduced as shown by the significantly lower values of serum pepsinogen and ostertagia antibody titres. The use of the bolus further reduced the adverse effects of parasitism as indicated by better liveweight gains and normal total plasma protein and albumin concentrations whereas in the untreated control group hypoproteinaemia and hypoalbuminaemia were observed. Most animals exhibited clinical signs of parasitic bronchitis at the end of the grazing season, and the bolus may not adequately control parasitic bronchitis in all cases at all times.

Animals↗
PubMed1991

Calcium and the malaria parasite: parasite maturation and the loss of red cell deformability.

In the studies reported here, we examined the role of calcium in the maturation of the human malaria parasite Plasmodium falciparum, and in the loss of red cell deformability associated with parasite maturation. P. falciparum alters the permeability of its host red cell, which normally maintains submicromolar cytoplasmic concentrations of calcium. Infection of the red cell and parasite maturation produce a 30-fold increase in calcium uptake. Both parasite maturation and the loss of red cell deformability are blocked by EGTA (by extracellular-free calcium concentrations less than or equal to 35 microM) and by other calcium antagonists. The loss of red cell deformability that occurs with parasite maturation is accompanied by alterations in the cytoskeletal proteins of parasitized red cells similar to those produced by the calcium ionophore A23187 (reductions in bands 2.1 [ankyrin], 4.1, and 5 [actin]). These results establish that parasite development and the loss of red cell deformability are calcium-dependent. They suggest that parasite-induced changes in the calcium permeability of the red cell activate endogenous transglutaminase activity by raising the free calcium concentration of the red cell cytoplasm.

Animals↗
PubMed1992

An hypothesis to explain why cell-mediated immunity alone can contain infections by certain intracellular parasites and how immune class regulation of the response against such parasites can be subverted.

Cells with a low density of parasite-specific antigens on their surface are postulated to be susceptible to a cell-mediated attack but not to effector mechanisms normally activated following the binding of specific antibody to the infected cell. It is further postulated that such infected cells normally induce a cell-mediated response, and that cells infected with slow-growing intracellular parasites have a low density of parasite-specific antigens on their surface. Despite these general postulates, cell-mediated immunity is not invariably induced following natural infection by certain slow-growing parasites, such as those responsible for leprosy, tuberculosis, and the leishmaniases, and antibody can be induced that is exclusive of a strong, cell-mediated response. It is proposed that certain events in such cases subvert the normal regulatory processes that control the class of immunity induced. In these cases, the parasite-infected cells, bearing a low representation of parasite antigens, induce antibody even though they are not susceptible to antibody-dependent effector mechanisms, and so they are not eliminated. In this case, chronic infection and uncontrolled growth of the parasite occurs, often with fatal consequences.

Animals↗
PubMed1990

Effect of temperature and host-parasite ratio on sex differentiation of Romanomermis iyengari (Welch), a mermithid parasite of mosquitoes.

The effect of temperature and host-parasite ratio on the percentage infection and sex differentiation of R. iyengari was studied. Significant differences were observed in the percentage infection due to different host-parasite ratios and temperatures. At 25 degrees and 30 degrees C, the host parasite ratio of 1:3 resulted in 86-92% infection of Culex quinquefasciatus larvae. At 20 degrees and 35 degrees C, a higher host-parasite ratio was required to get this level of infection. More number of post-parasites per mosquito larva emerged at 20 degrees (1.5-5.8) and 25 degrees C (1.9-6.3) than at 30 degrees (1.5-3.9) and 35 degrees C (1.6-3.6). More than 50% of the post-parasites were females at 20 degrees and 25 degrees, 30 degrees and 35 degrees C at 1:1-1:10, 1:1-1:4 and 1:1-1:3 host-parasite ratios, respectively.

Animals↗
PubMed1990

Genetic complexity of Plasmodium vivax parasites in individual human infections analyzed with monoclonal antibodies against variant epitopes on a single parasite protein.

Monoclonal antibodies against variant epitopes of a highly polymorphic protein (PV200) in schizonts of Plasmodium vivax have been used to analyze the variety of genetically distinct populations of parasites present in the peripheral blood of individual P. vivax infections in Sri Lanka. In 9 out of 10 isolates of freshly drawn P. vivax infected blood from different individuals, parasites of only 1 PV200 serotype was found within each individual infection, even though parasites were serotypically distinct between individuals. In 1 isolate parasite population, 3 distinct PV200 serotypes were identified. Thus, most P. vivax infections appeared to consist of a single genetically homogeneous population of parasites within the detection limits of the technique. The prevalence of P. vivax infections in an area of malaria transmission in southern Sri Lanka and the densities of oocysts in mosquitoes fed on P. vivax infected individuals indicated that parasite populations would be transmitted many times before encountering parasites of other origins, and that individual populations would tend to reduce to genetic homogeneity during transmission. These expectations are consistent with the high proportion of genetically homogeneous P. vivax isolates observed.

Adult↗
PubMed1991

Circumsporozoite protein gene from Plasmodium reichenowi, a chimpanzee malaria parasite evolutionarily related to the human malaria parasite Plasmodium falciparum.

We have cloned and sequenced the gene encoding the circumsporozoite (CS) protein of Plasmodium reichenowi a Plasmodium falciparum-like malaria parasite of chimpanzees. Comparison of the two CS proteins reveals both similarities and differences in these two evolutionarily related parasites that have adapted to different hosts. The P. reichenowi CS protein has a new repeat sequence, NVNP, in addition to the P. falciparum-like NANP and NVDP repeats. In the immunodominant TH2R and TH3R regions of the CS protein, the amino acid sequences are similar in both parasite proteins. The differences in the two proteins exist in domains around the conserved regions, Region I and Region II, which are otherwise conserved in the CS proteins of P. falciparum analyzed to date. Studies of parasite protein genes of evolutionarily related malaria parasites, together with other immunologic and biologic characteristics, will help better understand the evolution and host parasite relationship of malaria parasites and may provide a tool for identifying protein determinants for malaria vaccine development.

Amino Acid Sequence↗
PubMed1975

Parasite reproductive strategy and evolution of castration of hosts by parasites.

A modification of the Euler equation is used to describe a simple parasite life history in which survival decreases with age at a rate determined by mortality of the parasitized host. The advantages of castration of hosts by parasites are discussed using the modified equation in which castration is equivalent to reducing parasite virulence in the host to near zero or zero. It is suggested that castrating parasites can infest a wider range of hosts with higher mortality rates and that within parasite groups having castrating and noncastrating species, the former should infest hosts with higher mortality rates and relatively larger gonads.

Ecology↗
PubMedDate not supplied

Pasteuria thornei sp. nov. and Pasteuria penetrans sensu stricto emend., mycelial and endospore-forming bacteria parasitic, respectively, on plant-parasitic nematodes of the genera Pratylenchus and Meloidogyne.

Descriptions are presented of two members of the Pasteuria penetrans group of mycelial and endospore-forming bacteria, parasitic on plant-parasitic nematodes. In one case, the epithet P. penetrans sensu stricto emend. has now been limited to members of this group with cup-shaped sporangia and ellipsoidal endospores, parasitic primarily on the root-knot nematode Meloidogyne incognita. The second organism, with rhomboidal sporangia and nearly spherical endospores, which is parasitic primarily on the root-lesion nematode Pratylenchus brachyurus, is assigned to P. thornei sp. nov. An updated and emended description is offered of the genus Pasteuria Metchnikoff 1888 emend. The relationships are analysed among these two nematode parasites and the type species of this genus, P. ramosa Metchnikoff 1888, a parasite of cladoceran invertebrates. Because none of these microbes has been publicly reported to have been cultivated axenically, these relationships are based mainly on morphological, developmental, and pathological criteria.

Animals↗
PubMed1978

The effect of variations in host and parasite density on the level of parasitization of Lymnaea truncatula by Fasciola hepatica.

Groups of the snail Lymnaea truncatula, maintained at a range of spatial densities, were exposed to different densities of miracidia of Fasiola hepatica. The resulting degree of parasitization was measured 3--4 weeks after infection. The relationship between parasite densities and parasitization appeared to be curvilinear. The lower than expected parasitization at high parasite densities could be explained by the multiple infection of some snails by two or more miracidia. The level of parasitization was not related exponentially to the temperature at which infection was carried out. This was thought to be due to the inverse relationship between miracidial longevity and swimming speed, with respect to temperature. A depth of free water overlying a mud surface was an absolute requirement for miracidia to successfully infect snails.

Animals↗
PubMed1986

Quantification of parasite development in the host-parasite system Biomphalaria glabrata and Schistosoma mansoni.

The visceral mass of Biomphalaria glabrata uninfected or infected with Schistosoma mansoni was serially sectioned. The amount of hepatopancreas tissue and of parasite tissue was quantified. In pool-infected snails the volume of the whole visceral mass increased very significantly until week 6 and then decreased. Due to the growing parasites the volume of the visceral mass in infected snails was at most times higher when compared with uninfected snails of the same dimensions. Two weeks p.i. there was a permanent and significant increase of parasite tissue until week 6. During this time the amount of hepatopancreas tissue still increased. From this time onwards till week 12 the proportion of parasite tissue remained rather constant, indicating a kind of regulation, whereas the hepatopancreas tissue decreased to about one-third of the volume found in uninfected snails of the same shell diameter. Compared with infections by a single miracidium there was a significant increase in parasite tissue after infection with two miracidia. Infections with more miracidia (5, 10, and 20) gave no significant further increase. This also demonstrates a kind of regulation. Mortality rate, growth rate and egg production were studied during an infection period of 12 weeks.

Animals↗
PubMed1992

Niche breadth in parasites: an evolutionarily stable strategy model, with special reference to the protozoan parasite Leishmania.

A parasite's host range essentially defines its niche breadth, which, as foraging theory predicts, is influenced by resource availability. For parasites, the interaction of infection and transmission characteristics with host population dynamics determines host availability. An epidemiological model, involving two host types and describing competition between a "generalist" parasite strain and a related "specialist" strain, is used to examine the interplay among host range, relative host availabilities, and adaptational compromises engendered by increased host range. Results show that the generalist can predominate even when it cannot maintain itself in either host alone, but that the specialist can persist if its reproductive rate attains some threshold relative to either of the generalist's respective rates in its two hosts. The model is in rough, qualitative agreement with observed dynamics of two Leishmania parasite-host systems, and overall results suggest that infection of two species with a common parasite can lead to complex, indirect coevolutionary dynamics.

Adaptation, Biological↗
PubMed1991

Sexual showiness and parasite load: correlations without parasite coevolutionary cycles.

Hamilton & Zuk (1982, Science 218, 384-387.) produced a model of sexual selection in which coevolutionary cycles of host and parasites generate consistently positive correlations between parent and offspring viability, and that animals choose mates for genetic disease resistance by scrutinizing characters whose full expression is dependent on health and vigour. They predicted a positive correlation between sexual showiness and parasite burden across species, and a negative correlation within a species. First, recent suggestions that interspecific correlations in the opposite direction to that indicated above are consistent with the mechanisms of Hamilton & Zuk's model are discussed. Second, it is shown that the model's predictions can be produced by heritable variation maintained by non-parasite fluctuating selection. In this case, the parasites associated with degree of sexual showiness are those able to amplify any initial heritable differences in vigour. Alternative sources of positive correlation between parent and offspring viability, which include the indirect effects of climatic change and exclude the need for host-parasite coevolutionary cycles, are also proposed.

Animals↗
PubMed1989

Use of a DNA probe to analyse the dynamics of infection with rodent malaria parasites confirms that parasite clearance during crisis is predominantly strain- and species-specific.

A DNA probe, PCsv4.1, isolated from Plasmodium chabaudi chabaudi AS, generates in Southern blotting experiments restriction fragment length polymorphisms specific to a particular rodent malaria parasite line. It was used to develop an assay which allows identification and semi-quantitative compositional analysis of sample parasite populations in which one or more strains, subspecies or species were present. In experiments where mechanisms effecting parasite clearance during crisis were studied, the assay was used to determine the composition of parasite populations present in P. c. chabaudi AS infected mice challenged during crisis with homologous or heterologous parasites. It was thus confirmed that clearance mechanisms during crisis operate in a predominantly specific manner.

Animals↗
PubMed1975

[Glutathionestatus of Plasmodium vinckei parasitized erythrocytes in correlation to the intraerythrocytic development of the parasite (author's transl)].

The glutathione status of Plasmodium vinckei parasitized erythrocytes of mice was determined in correlation to the intraerythrocytic stage of maturation of the parasite. The different stages of blood schizogony were separated by discontinuous Dextran-density-centrifugation. The changes of protein content, glutathione concentration (reduced/oxidized and bound/free glutathione) and in the specific activities of the following enzymes: gamma-glutamyl-cysteine-synthetase (GC-synthetase), glutathione-reductase (GR), glucose-6-phosphate dehydrogenase (Gl-DH), glutathione-peroxydase (G-POD) and catalase were investigated in dependence of the intraerythrocytic stage of development. The following changes of the investigated metabolic parameters were observed during the schizogony: - the protein content decreased to about one half, - the glutathione concentration increased about 10-fold, while the relations reduced/oxidized and free/bound glutathione remained constant, - Gl-DH activity appeared and increased steeply, - the specific activities of GC-synthetase and of GR increased more than 2-fold, while G-POD remained almost constant, - and the activities of G-6-PDH and catalase showed a significant, strong decrease to about 25% of the original values. It is tried to relate the observed changes to the growing parasite or to the host cell. The significance of the results for the metabolism of malaria parasites and for a possible adaptation to the mosquito by a GSH mediated protection of the malaria parasite against an enzymatic defence-reaction of the mosquito, is discussed.

Animals↗
PubMed1987

The bovine autologous Theileria mixed leucocyte reaction: influence of monocytes and phenotype of the parasitized stimulator cell on proliferation and parasite specificity.

In the autologous Theileria mixed leucocyte reaction (MLR), irradiated Theileria parva-infected cells induce proliferative responses in autologous peripheral blood mononuclear leucocytes (PBM), irrespective of the immune status of the donor animal. In this paper we have analysed the cellular basis of this response in naive and immune cattle to determine the Theileria specificity of the response. The magnitude of proliferation is dependent on two parameters, namely the presence or absence of monocytes in the responder population, and the phenotype of the parasitized stimulator cells, both of which appeared to be independent of the immune status of the donor animal. Monocyte-depleted responders invariably gave stronger proliferative responses but generated cytotoxicity from immune cattle that tended to be less genetically restricted. Marked differences were observed in the stimulatory capacity of cloned parasitized T-cell and non-T cell lines. At least part of this variation was associated with differences in the capacity of the parasitized cells to secrete soluble suppressive factors and possibly also stimulatory factors. Two observations indicated that, in immune cattle, part of the proliferative response in the autologous Theileria MLR is parasite-specific. First, stimulator cells fixed with glutaraldehyde stimulated proliferative responses in monocyte depleted PBM from immune animals but not naive animals. Second, in autologous Theileria MLRs with intact PBM, genetically restricted cytotoxic cells were generated from immune but not naive animals. While monocytes seem not to be required for induction of the parasite-specific component of the response, their absence from the assay when viable stimulator cells are utilized appears to enhance the non-specific component of the proliferative and cytotoxic responses.

Animals↗