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Biomedical subjects

R Poulin

Publications and source records attributed to R Poulin.

At least 19 recordsLinked to original sources

Synthesis of spermidine and norspermidine dimers as high affinity polyamine transport inhibitors.

A series of novel spermidine and sym-norspermidine dimers was synthesized by crosslinking the polyamine backbones via alkylation of their secondary amino groups to butyl, trans-2-butenyl, 2-butynyl or p-xylyl bridges. The resulting hexamines behaved as high-affinity antagonists of polyamine uptake, with a relative potency that was dependent on the geometry of the linker structure.

Biological Transport

Aggregation and species coexistence of ectoparasites of marine fishes.

Interspecific interaction may lead to species exclusion but there are several ways in which species can coexist. One way is by reducing the overall intensity of competition via aggregated utilisation of fragmented resources. Known as the 'aggregation model of coexistence', this system assumes saturation and an equilibrium number of species per community. In this study we tested the effects of interspecific aggregation on the level of intraspecific aggregation among ectoparasites of marine fishes (36 communities of gill and head ectoparasite species). If parasite species are distributed in a way that interspecific aggregation is reduced relative to intraspecific aggregation then species coexistence is facilitated. We found a positive relationship between parasite species richness and fish body size, controlling for host phylogeny. A positive relationship between infracommunity species richness and total parasite species richness was also found, providing no evidence for saturation. This result supports the view that infracommunities of parasites are not saturated by local parasite residents. The observed lack of saturation implies that we are far from a full exploitation of the fish resource by parasites. Ectoparasites were aggregated at both population and species levels. However, only half of the ectoparasite communities were dominated by negative interspecific aggregation. We found that infracommunity parasite species richness was positively correlated with the level of intraspecific aggregation versus interspecific aggregation. This means that intraspecific aggregation increases compared with interspecific aggregation when total parasite species richness increases, controlling fish size and phylogeny. This supports one assumption of the 'aggregation model of coexistence', which predicts that interspecific interactions are reduced relative to intraspecific interactions, facilitating species coexistence.

Animals

The functional importance of parasites in animal communities: many roles at many levels?

Past research on parasites and community ecology has focussed on two distinct levels of the overall community. First, it has been shown that parasites can have a role in structuring host communities. They can have differential effects on the different hosts that they exploit, they can directly debilitate a host that itself is a key structuring force in the community, or they can indirectly alter the phenotype of their host and change the importance of the host for the community. Second, certain parasite species can be important in shaping parasite communities. Dominant parasite species can directly compete with other parasite species inside the host and reduce their abundance to some extent, and parasites that alter host phenotype can indirectly make the host more or less suitable for other parasite species. The possibility that a parasite species simultaneously affects the structure of all levels of the overall community, i.e. the parasite community and the community of free-living animals, is never considered. Given the many direct and indirect ways in which a parasite species can modulate the abundance of other species, it is conceivable that some parasite species have functionally important roles in a community, and that their removal would change the relative composition of the whole community. An example from a soft-sediment intertidal community is used to illustrate how the subtle, indirect effects of a parasite species on non-host species can be very important to the structure of the overall community. Future community studies addressing the many potential influences of parasites will no doubt identify other functionally important parasite species that serve to maintain biodiversity.

Animals

Phenotypic variability induced by parasites:.

The diversity of ways in which parasites can modify the host genotypic signal has been documented in recent years. For example, parasites can shift the mean value and increase the variance of phenotypic traits in host populations, or alter the phenotypic sex ratio of host populations, with several evolutionary implications. Here, Robert Poulin and Frederic Thomas review the types of host traits that are modified by parasites, then explore some of the evolutionary consequences of parasite-induced alterations in host phenotypes and suggest some avenues for future research.

Animals

Elevated levels of polyamines and trypanothione resulting from overexpression of the ornithine decarboxylase gene in arsenite-resistant Leishmania.

The levels of trypanothione, a glutathione-spermidine conjugate, are increased in the protozoan parasite Leishmania selected for resistance to the heavy metal arsenite. The levels of putrescine and spermidine were increased in resistant mutants. This increase is mediated by overexpression of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. Gene overexpression is generally mediated by gene amplification in Leishmania but, here, the mRNA and the enzymatic activity of ODC are increased without gene amplification. This RNA overexpression is stable when cells are grown in the absence of the drug and does not result from gene rearrangements or from an increased rate of RNA synthesis. Transient transfections suggest that mutations in the revertant cells contribute to these elevated levels of RNA. Stable transfection of the ODC gene increases the level of trypanothione, which can contribute to arsenite resistance. In addition to ODC overexpression, the gene for the ABC transporter PGPA is amplified in the mutants. The co-transfection of the ODC and PGPA genes confers resistance in a synergistic fashion in partial revertants, also suggesting that PGPA recognizes metals conjugated to trypanothione.

Animals

Stabilization of disease as a useful predictor of survival following second-line chemotherapy in small cell lung cancer and ovarian cancer patients.

To assess the value of disease stabilization (SD) as a predictor of survival following chemotherapy, data were analyzed from multicenter clinical trials in small cell lung cancer (SCLC) and ovarian cancer (OC) patients receiving various second-line chemotherapy regimens. In both patient populations, SD (lasting >8 weeks) and partial responses (PR) were associated with a survival benefit versus progressive disease (PD); interestingly, the survival benefit was similar between the two groups (PR and SD). These results suggest that, at least in these populations, SD may represent a potential benefit of chemotherapy and therefore the distinction between SD and PR may not be useful.

Adult

Dependence of mammalian putrescine and spermidine transport on plasma-membrane potential: identification of an amiloride binding site on the putrescine carrier.

The mechanism of mammalian polyamine transport is poorly understood. We have investigated the role of plasma-membrane potential (DeltaPsipm) in putrescine and spermidine uptake in ZR-75-1 human breast cancer cells. The rate of [3H]putrescine and [3H]spermidine uptake was inversely correlated to extracellular [K+] ([K+]o) and to DeltaPsipm, as determined by the accumulation of [3H]tetraphenylphosphonium bromide (TPP). Inward transport was unaffected by a selective decrease in mitochondrial potential (DeltaPsimit) induced by valinomycin at low [K+]o, but was reduced by approximately 60% by the rheogenic protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP), which rapidly (<=15 min) collapsed both DeltaPsipm and DeltaPsimit. Plasma-membrane depolarization by high [K+]o or CCCP did not enhance putrescine efflux in cells pre-loaded with [3H]putrescine, suggesting that decreased uptake caused by these agents did not result from a higher excretion rate. On the other hand, the electroneutral K+/H+ exchanger nigericin (10 microM) co-operatively depressed -3H-TPP, [3H]putrescine and [3H]spermidine uptake in the presence of ouabain. Suppression of putrescine uptake by nigericin+ouabain was Na+-dependent, suggesting that plasma-membrane repolarization by the electrogenic Na+ pump was required upon acidification induced by nigericin, due to the activation of the Na+/H+ antiporter. The sole addition of 5-N, N-hexamethylene amiloride, a potent inhibitor of the Na+/H+ antiporter, strongly inhibited putrescine uptake in a competitive fashion -Ki 4.0+/-0.9 (S.D.) microM-, while being a weaker antagonist of spermidine uptake. The potency of a series of amiloride analogues to inhibit putrescine uptake was clearly different from that of the Na+/H+ antiporter, and resembled that noted for Na+ co-transport proteins. These data demonstrate that putrescine and spermidine influx is mainly unidirectional and strictly depends on DeltaPsipm, but not DeltaPsimit. This report also provides first evidence for a high-affinity amiloride-binding site on the putrescine carrier, which provides new insight into the biochemical properties of this transporter.

Amiloride

The spermidine transport system is regulated by ligand inactivation, endocytosis, and by the Npr1p Ser/Thr protein kinase in Saccharomyces cerevisiae.

We have characterized the regulation of spermidine transport in yeast and identified some of the genes involved in its control. Disruption of the SPE2 gene encoding S-adenosylmethionine decarboxylase, which catalyzes an essential step in polyamine biosynthesis, upregulated the initial velocity of spermidine uptake in wild-type cells as well as in the polyamine transport-deficient pcp1 mutants. Exogenous spermidine rapidly inactivated spermidine transport with a half-life of approximately 10-15 min via a process that did not require de novo protein synthesis but was accelerated by cycloheximide addition. Conversely, reactivation of spermidine influx upon polyamine deprivation required active protein synthesis. The stability of polyamine carrier activity was increased 2-fold in polyamine-depleted spe2 deletion mutants, indicating that endogenous polyamines also contribute to the down-regulation of spermidine transport. Ligand-mediated repression of spermidine transport was delayed in end3 and end4 mutants that are deficient in the initial steps of the endocytic pathway, and spermidine uptake activity was increased 4- to 5-fold in end3 mutants relative to parental cells, although the stability of the transport system was similar in both strains. Disruption of the NPR1 gene, which encodes a putative Ser/Thr protein kinase essential for the reactivation of several nitrogen permeases, resulted in a 3-fold decrease in spermidine transport in NH4(+)-rich media but did not prevent its down-regulation by spermidine. The defect in spermidine transport was more pronounced in NH4(+)- than proline-grown npr1 cells, suggesting that NPR1 protects against nitrogen catabolite repression of polyamine uptake activity. These results suggest that (a) the polyamine carrier is an unstable protein subject to down-regulation by spermidine via a process involving ligand inactivation followed by endocytosis and that (b) NPR1 expression fully prevents nitrogen catabolite repression of polyamine transport, unlike the role predicted for that gene by the inactivation/reactivation model proposed for other nitrogen permeases.

Biological Transport

Exploitation of manipulators: 'hitch-hiking' as a parasite transmission strategy.

For many parasites with complex life cycles, manipulation of host behaviour is an adaptation to increase the probability of successful transmission. Since manipulation is likely to be costly, other parasites may exploit hosts already manipulated so as to ensure their transmission without investing in manipulation. Such a cheating strategy, called 'hitch-hiking', could be adaptive in a range of situations. We first propose and discuss criteria that should be met by any parasite to be considered a hitch-hiker. Then, to understand the evolution of the hitch-hiking strategy, we use simple mathematical models to analyse the influence of several variables on the potential benefits for a nonmanipulative parasite of actively seeking a ride to the definitive host with a manipulative parasite. The models suggest that the prevalence or abundance of manipulative parasites will be a key determinant of whether hitch-hiking can be an advantageous option for other parasites. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article

Parasite extinction and colonisation and the evolution of parasite communities: a simulation study.

We determined what evolutionary processes influence the likelihood of detecting an effect of host ecological characteristics on the richness of parasite communities in comparative analyses among related host species. We used a mathematical model to generate phylogenies of hosts in which parasite communities varied over evolutionary time as parasite species were either gained or lost during host speciation events. Gain or loss of parasites were stochastic and could either be strongly, moderately, weakly, or not, affected by host ecological characteristics. The model was evaluated over this range of effects of host ecology, and for various mean probabilities of parasite gain and loss and various rates of change in host ecological characteristics at speciation events. Our results suggest that phylogenetic effects (the passing of parasite species from mother to daughter host species) are likely to obscure ecological effects (the effect of host body size, diet, habitat, lifespan, etc.) except when the effects of host ecology are strong, and the probabilities of gain or loss of parasites are high, or host ecological characteristics change markedly at speciation events. This outcome was not influenced by the shape of the phylogenetic tree used in the simulations. Sensitivity analysis of our model also shows this result to be robust to a wide range of assumptions and parameter values. Thus, because the composition of parasite communities tends to reflect their ancestry, the effect of host ecology will often be very difficult to detect.

Animals

Evolution and phylogeny of behavioural manipulation of insect hosts by parasites.

The literature contains many examples of changes induced by parasites in the behaviour and/or other phenotypic traits of insects. From an evolutionary perspective, the nature of these changes is usually difficult to assess. Parasite-induced changes in host behaviour can be adaptations of either host or parasite, or they can be mere pathological consequences of infection. Of the many criteria and experimental tests necessary to distinguish between adaptations and non-selected consequences, two are particularly important: the demonstration of fitness benefits for either host or parasite associated with the behavioural change, and the elucidation of the proximate mechanism responsible for the behavioural change. Another approach can serve to identify adaptive changes in behavior: mapping specific behavioural alterations on a phylogeny of either hosts or parasites. The usefulness of this approach is illustrated with two examples, acanthocephalan-cockroach associations and insect-fungus associations. The adaptive nature of parasite-induced behavioural changes will always be difficult to evaluate because they are the product of two distinct but interacting genotypes. However, experimental and phylogenetic approaches can provide valuable insights into the evolutionary history of insect-parasite interactions.

Acanthocephala

Manipulation of a mollusc by a trophically transmitted parasite: convergent evolution or phylogenetic inheritance?

We investigated the influence of infection by the trematode Curtuteria australis on the burrowing behaviour of its intermediate host, the bivalve Austrovenus stutchburyi. Laboratory experiments and field observations revealed that cockles, unable to bury completely or even partially under the sediment, have a reduced foot length compared with buried individuals. The ability to bury proved to be highly repeatable in field experiments: cockles found at the surface and transplanted to an experimental area did not bury themselves, and cockles found buried stayed buried when relocated. All metacercariae of C. australis were found strictly in the foot and for each of 3 samples collected in different sites, there was a negative and significant relationship between the relative length of the foot and the parasite load. A predation test conducted under natural conditions indicated that cockles with the stunted foot and the altered behaviour are significantly more susceptible to predation by aquatic birds than other cockles. Given that the definitive host of C. australis is an oystercatcher, we first discuss our results in the context of transmission strategy. Comparisons with other studies on more or less related trematode species parasitic in bivalves and evolving under similar constraints for their transmission, shed light on the origin of this adaptation in C. australis.

Animals

Comparison of three estimators of species richness in parasite component communities.

Comparisons of species richness between parasite component communities are often confounded by uneven sampling effort and the possibility that rare species have been missed from some component communities. The use of nonparametric estimators of species richness could potentially alleviate this problem by allowing the number of missing species to be extrapolated from the observed data. The performance of 3 estimators and their sensitivity to true species richness and the frequency of rare species, i.e., species with low prevalence, were tested using computer-simulated parasite communities. When the number of hosts examined in a sample is large, the observed species richness is an accurate estimate of true richness; no extrapolation is necessary even when rare species make up a large part of the community. At small sample sizes, observed species richness is a poor underestimate of true richness. The jackknife estimator and Chao's estimator both improve the estimate of species richness, but they are imprecise and can seriously overshoot the true richness value when the community includes many rare species. The bootstrap estimator. on the other hand, gives a better estimate than observed richness. Bootstrap estimates are also less variable and less likely to overestimate true richness, independently of how frequent rare species are in the community. This estimator provides a better, but conservative, estimate of true richness than observed richness and should be used to correct for inadequate host sampling. Data from natural communities suggest that the use of richness estimators is often justified, and that many parasite species may regularly escape detection.

Animals

Hosts manipulated by one parasite incur additional costs from infection by another parasite.

Manipulation of host phenotype by parasites often serves to increase the predation rate of definitive hosts on intermediate hosts. For intermediate hosts, the indirect consequences of manipulation may extend beyond the direct increase in predation, however. Metacercariae of the trematode Curtuteria australis encyst in the foot of New Zealand cockles, Austrovenus stutchburyi, and stunt its growth, rendering cockles incapable of burrowing into the sediments. Here, we show that cockles manipulated by C. australis are 5 times more likely to be infected by the castrating sporocysts of another trematode than normal, nonmanipulated cockles. Our results indicate that the consequences for C. australis-manipulated cockles are far more important than a simple increase in the risk of predation and that indirect repercussions of manipulation can be as severe as direct ones.

Animals

Nonmanipulative parasites in manipulated hosts: 'hitch-hikers' or simply 'lucky passengers'?

Manipulation of intermediate host behavior to favor parasitic transmission has been demonstrated in a wide of range of parasitic taxa. Recent advances in parasitology have suggested that nonmanipulative parasite species can obtain a high probability of transmission simply by infecting hosts already manipulated ('hitch-hiker' parasites). In this study, from a field collection of Gammarus aequicauda (Amphipoda, second intermediate host), we analyzed the ecological association between the manipulative trematode Microphallus papillorobustus and the 2 nonmanipulative trematodes Microphallus hoffmanni and Levinseniella tridigitata. Although these 2 nonmanipulative parasites should be a priori advantaged when infecting manipulated gammarids, there was no significant ecological association between parasite species. We discuss the possible reasons why these 2 nonmanipulative parasites are only 'lucky passengers' rather than 'hitch-hikers.'

Animals

Parasite body size distributions: interpreting patterns of skewness.

We examined the distributions of log body sizes of parasite species to test the prediction that the different physical constraints acting on endoparasites and ectoparasites can lead to different size distributions, and to see whether the distributions of parasite body sizes differ from those of free-living animals. We used body size distributions from 19 groups of parasitic of free-living animals, including over 7000 species and almost 2400 genera. There were differences between the body size distributions of male and female parasites, and between the body size distributions of related parasites exploiting different types of hosts. In general, parasite body size distributions were less frequently log right skewed than those of free-living animals. Ectoparasites tended to have more symmetric body size distributions than endoparasites, in which the most speciose size classes tended to be the smaller ones. Severe space constraints and a greater diversity of small niches may only allow the diversification of small endoparasites, whereas ectoparasite body sizes may face less severe limitations.

Animals