scholarly journals Common host variation drives malaria parasite fitness in healthy human red cells

2020 ◽  
Author(s):  
Emily R Ebel ◽  
Frans A Kuypers ◽  
Carrie Lin ◽  
Dmitri A Petrov ◽  
Elizabeth S Egan
Keyword(s):  
Growth Rate ◽  
African Ancestry ◽  
Severe Disease ◽  
Parasite Growth ◽  
Hydration Status ◽  
Healthy Human ◽  
Parasite Fitness ◽  
Deleterious Alleles ◽  
Pathogenic Variation ◽  
Parasite Replication

SUMMARYThe replication of Plasmodium falciparum parasites within red blood cells (RBCs) causes severe disease in humans, especially in Africa. The influence of host RBC variation on parasite replication is largely uncharted, aside from a handful of deleterious alleles like sickle cell. Here, we integrated analyses of exome sequencing, RBC phenotyping, and parasite fitness assays on blood from 122 individuals, most with African ancestry. In donors lacking alleles for hemoglobinopathies or G6PD deficiency, RBC phenotypes including size, deformability, and hydration status explained 21-38% of the variation in parasite growth rate. With the addition of non-pathogenic polymorphisms in 14 RBC proteins including SPTA1, PIEZO1, and ATP2B4, our model explained 73-82% of the variation in parasite growth rate. Interestingly, we observed little evidence for divergent selection on this variation between Africans and Europeans. These findings suggest a model in which widespread, non-pathogenic variation in a moderate number of genes strongly modulates P. falciparum fitness in RBCs.

scholarly journals Common host variation drives malaria parasite fitness in healthy human red cells

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Emily R Ebel ◽  
Frans A Kuypers ◽  
Carrie Lin ◽  
Dmitri A Petrov ◽  
Elizabeth S Egan
Keyword(s):  
Growth Rate ◽  
African Ancestry ◽  
Severe Disease ◽  
Negative Evidence ◽  
Fresh Blood ◽  
Healthy Human ◽  
Parasite Fitness ◽  
Deleterious Alleles ◽  
Healthy Donors ◽  
Common Genetic Variants

The replication of Plasmodium falciparum parasites within red blood cells (RBCs) causes severe disease in humans, especially in Africa. Deleterious alleles like hemoglobin S are well-known to confer strong resistance to malaria, but the effects of common RBC variation are largely undetermined. Here we collected fresh blood samples from 121 healthy donors, most with African ancestry, and performed exome sequencing, detailed RBC phenotyping, and parasite fitness assays. Over one third of healthy donors unknowingly carried alleles for G6PD deficiency or hemoglobinopathies, which were associated with characteristic RBC phenotypes. Among non-carriers alone, variation in RBC hydration, membrane deformability, and volume was strongly associated with P. falciparum growth rate. Common genetic variants in PIEZO1, SPTA1/SPTB, and several P. falciparum invasion receptors were also associated with parasite growth rate. Interestingly, we observed little or negative evidence for divergent selection on non-pathogenic RBC variation between Africans and Europeans. These findings suggest a model in which globally widespread variation in a moderate number of genes and phenotypes modulates P. falciparum fitness in RBCs.

scholarly journals Interaction of Plasmodium falciparum apicortin with α- and β-tubulin is critical for parasite growth and survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Malabika Chakrabarti ◽  
Nishant Joshi ◽  
Geeta Kumari ◽  
Preeti Singh ◽  
Rumaisha Shoaib ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Life Cycle ◽  
Specific Protein ◽  
Parasite Growth ◽  
Growth And Survival ◽  
Apicomplexan Parasites ◽  
Parasite Replication ◽  
Main Components ◽  
Β Tubulin

AbstractCytoskeletal structures of Apicomplexan parasites are important for parasite replication, motility, invasion to the host cell and survival. Apicortin, an Apicomplexan specific protein appears to be a crucial factor in maintaining stability of the parasite cytoskeletal assemblies. However, the function of apicortin, in terms of interaction with microtubules still remains elusive. Herein, we have attempted to elucidate the function of Plasmodium falciparum apicortin by monitoring its interaction with two main components of parasite microtubular structure, α-tubulin-I and β-tubulin through in silico and in vitro studies. Further, a p25 domain binding generic drug Tamoxifen (TMX), was used to disrupt PfApicortin-tubulin interactions which led to the inhibition in growth and progression of blood stage life cycle of P. falciparum.

scholarly journals The SARS-CoV-2 Alpha variant is associated with increased clinical severity of disease

2021 ◽  
Author(s):  
David J Pascall ◽  
Guy Mollett ◽  
Rachel Blacow ◽  
Naomi Bulteel ◽  
Robyn Campbell ◽  
...  
Keyword(s):  
Growth Rate ◽  
Cohort Study ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Transmission Rate ◽  
Severe Disease ◽  
Positive Association ◽  
Clinical Severity ◽  
Generalised Linear Mixed Model ◽  
The Impact

Background The Alpha (B.1.1.7) SARS-CoV-2 variant of concern has been associated with increased transmission and increased 28-day mortality. We aimed to investigate the impact of infection on clinical severity of illness, including the need for oxygen or ventilation in a national cohort study. Methods In this prospective clinical cohort study, 1475 SARS-CoV-2 sequences were obtained from patients infected in Scotland, UK between the 1st November 2020 and 30th January 2021 and matched to clinical outcomes as the lineage became dominant in Scotland. We modelled the association between B.1.1.7 infection and severe disease using a cumulative generalised linear mixed model employing a 4-point scale of maximum severity based on requirement of respiratory support at 28 days. We also estimated the growth rate of B.1.1.7-associated infections as it emerged in Scotland using a phylogenetic exponential growth rate population model. Results The B.1.1.7 lineage was responsible for a third wave of SARS-CoV-2 infection in Scotland in association with a transmission rate 5-fold higher than the preceding second wave B.1.177 lineage. Of 1475 patients, 364 were infected with B.1.1.7, 1030 with B.1.177 and 81 with other lineages. Our analysis found a positive association between increased clinical severity and lineage (B.1.1.7 versus non-B.1.1.7; cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93). Viral load was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold (Ct) value (mean Ct change: -2.46, 95% CI: -4.22, -0.70). Conclusions The B.1.1.7 lineage was associated with more severe clinical disease in Scottish patients than co-circulating lineages.

scholarly journals Toxoplasma gondiisalvages sphingolipids from the host Golgi through the rerouting of selected Rab vesicles to the parasitophorous vacuole

2013 ◽  
Vol 24 (12) ◽  
pp. 1974-1995 ◽  
Author(s):  
Julia D. Romano ◽  
Sabrina Sonda ◽  
Emily Bergbower ◽  
Maria Elisa Smith ◽  
Isabelle Coppens
Keyword(s):  
Toxoplasma Gondii ◽  
Mammalian Cells ◽  
De Novo ◽  
Parasitophorous Vacuole ◽  
Parasite Growth ◽  
Sphingolipid Metabolism ◽  
Obligate Intracellular ◽  
Membrane Bound ◽  
Parasite Replication

The obligate intracellular protozoan Toxoplasma gondii actively invades mammalian cells and, upon entry, forms its own membrane-bound compartment, named the parasitophorous vacuole (PV). Within the PV, the parasite replicates and scavenges nutrients, including lipids, from host organelles. Although T. gondii can synthesize sphingolipids de novo, it also scavenges these lipids from the host Golgi. How the parasite obtains sphingolipids from the Golgi remains unclear, as the PV avoids fusion with host organelles. In this study, we explore the host Golgi–PV interaction and evaluate the importance of host-derived sphingolipids for parasite growth. We demonstrate that the PV preferentially localizes near the host Golgi early during infection and remains closely associated with this organelle throughout infection. The parasite subverts the structure of the host Golgi, resulting in its fragmentation into numerous ministacks, which surround the PV, and hijacks host Golgi–derived vesicles within the PV. These vesicles, marked with Rab14, Rab30, or Rab43, colocalize with host-derived sphingolipids in the vacuolar space. Scavenged sphingolipids contribute to parasite replication since alterations in host sphingolipid metabolism are detrimental for the parasite's growth. Thus our results reveal that T. gondii relies on host-derived sphingolipids for its development and scavenges these lipids via Golgi-derived vesicles.

scholarly journals The effect of salinity on transovarial transmission of a microsporidian infecting Gammarus duebeni

Parasitology ◽  
1997 ◽  
Vol 115 (4) ◽  
pp. 381-385 ◽  
Author(s):  
A. M. DUNN ◽  
M. J. HATCHER
Keyword(s):  
Parasite Burden ◽  
Parasite Growth ◽  
Lower Proportion ◽  
Follicle Cells ◽  
Transovarial Transmission ◽  
Parasite Transmission ◽  
Gonotrophic Cycle ◽  
Elevated Salinity ◽  
Parasite Replication ◽  
The Impact

This is an investigation of the impact of salinity on transovarial transmission and burden of a microsporidian sex ratio distorter in the inter-tidal crustacean Gammarus duebeni. Exposure of parasitized mothers to increased salinity during the gonotrophic cycle caused an increase in parasite burden in the follicle cells and a decrease in burden in the oocytes. It appears that salinity impedes parasite transmission from the follicle cells to the oocytes during host oogenesis. A lower proportion of the young were infected in broods from elevated salinity and, in infected offspring, parasite burden was lower than in control embryos. Parasite replication occurred during embryogenesis. However, the pattern of parasite growth did not differ between salinities, indicating that differences in parasite burden could be attributed to a reduction in the initial parasite burden transmitted to the gamete, rather than to a reduction in parasite replication during host embryogenesis. We discuss our findings with respect to parasite/host dynamics and the ecology of the host.

Growth of Trypanosoma cruzi in vitro: development and application of a continuous-flow culture system

Parasitology ◽  
1982 ◽  
Vol 84 (3) ◽  
pp. 511-526 ◽  
Author(s):  
G. T. Williams ◽  
L. Hudson
Keyword(s):  
Growth Rate ◽  
Trypanosoma Cruzi ◽  
Continuous Flow ◽  
Culture System ◽  
Extreme Values ◽  
Environmental Parameters ◽  
Optimal Growth ◽  
Parasite Growth ◽  
Vitro Development

SummaryThe design and operation of a modular, bacteriological continuous-flow culture system have been adapted for the growth of Trypanosoma cruzi epimastigotes in simple monophasic media. The system was designed to achieve a minimum of 200 days of continuous culture and provision was made for the continuous supply of medium and collection of parasites under sterile conditions. The system provides large quantities of epimastigotes with homogeneous morphology and uniform viability. The system also lends itself tothe analysis of the factors which affect parasite growth. We have examined the effects of changes in environmental parameters on epimastigote growth rate. Optimal growth was observed at 27 °C. The rate ofstirring of the culture had a small but definable effect on the growth rate, which was greatest at 80 r.p.m. Growth was only slightly affected by the level of dissolved oxygen between 10 and 50% saturation, but was inhibited at higher concentrations. Growth was slower at extreme values of pH but showed a broad optimum around pH 7·4.

Spontaneous variability of single isolates of Phytophthora infestans. II. Pathogenic variation

1970 ◽  
Vol 48 (5) ◽  
pp. 897-905 ◽  
Author(s):  
C. E. Caten
Keyword(s):  
Growth Rate ◽  
Generation Time ◽  
High Growth ◽  
High Growth Rate ◽  
R Gene ◽  
Physiologic Race ◽  
Pathogenic Variation ◽  
Resistant Varieties ◽  
Selection For ◽  
Physiologic Races

The variation in two aspects of pathogenicity, aggressiveness and virulence (physiologic race), among single zoospore cultures from three wild isolates has been examined. Two components of aggressiveness were measured, rate of growth on tubers and generation time on detached leaflets. Virulence was assessed from the pattern of compatible and incompatible reactions to members of the R gene differential series. Extensive variation in aggressiveness was detected in samples of zoospore cultures from all three isolates. The level of aggressiveness ranged from a high, equivalent to that of the parental wild isolates, to a complete lack of pathogenicity; as much as 45% was of the latter type. No instance of a change in virulence was found among 104 cultures tested.The significance of the observed pathogenic variation is discussed. It is concluded that zoospore variation is not important as a source of new physiologic races or strains adapted to particular, horizontally resistant varieties. Comparison of populations of zoospore cultures with samples of wild isolates suggests that directional selection for high growth rate and high and rapid sporulation operates in nature. The correlations between a number of cultural and pathogenic characters are examined, and an association between abundant sporulation in culture and high aggressiveness demonstrated.

A study of the effect of temperature on the growth of Fasciola hepatica in Lymnaea truncatula

Parasitology ◽  
1974 ◽  
Vol 68 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Nigel G. Nice ◽  
R. A. Wilson
Keyword(s):  
Growth Rate ◽  
Fasciola Hepatica ◽  
Meteorological Data ◽  
Snail Host ◽  
Parasite Growth ◽  
Effect Of Temperature ◽  
Lymnaea Truncatula ◽  
Relationship Of ◽  
Environmental Temperatures ◽  
Simulation Equation

The growth rates of the intramolluscan stages of the parasite Fasciola hepatica were determined at three temperatures 16°, 20° and 25°C. A graphical relationship of growth rate with respect to temperature was produced and a growth array was calculated from this. Meteorological data were summarized in the form of a temperature array. These arrays were then used in conjunction with a simple equation to simulate parasite growth within the snail host. A digital computer was employed to solve iteratively the simulation equation, initially by checking its application against experimentally determined results. It was then employed with the meteorological data to simulate growth with respect to environmental temperatures and the results obtained were compared with those derived from field collections. Estimates were also made of the duration of the shortest life-cycle under field conditions.

scholarly journals Comparison of statistical models to estimate parasite growth rate in the induced blood stage malaria model

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Leesa F. Wockner ◽  
Isabell Hoffmann ◽  
Peter O’Rourke ◽  
James S. McCarthy ◽  
Louise Marquart
Keyword(s):  
Growth Rate ◽  
Statistical Models ◽  
Parasite Growth ◽  
Blood Stage ◽  
Malaria Model ◽  
Blood Stage Malaria

Variation in pathogenicity and virulence of Phytophthora clandestina on four cultivars of subterranean clover

1995 ◽  
Vol 35 (6) ◽  
pp. 717 ◽  
Author(s):  
A Purwantara ◽  
SP Flett ◽  
PJ Keane
Keyword(s):  
Growth Rate ◽  
Agar Medium ◽  
Sandy Loam ◽  
Severe Disease ◽  
Subterranean Clover ◽  
Race 1 ◽  
Pathogenicity Tests ◽  
Loam Soil ◽  
Race 2 ◽  
Cultivar Specificity

The pathogenicity of 6 isolates of Phytophthora clandestina on seedlings of 4 cultivars of subterranean clover was studied. There was a highly significant isolate x cultivar interaction in pathogenicity tests on axenic seedlings and seedlings grown in pasteurised potting mix or untreated sandy loam soil, indicating the existence of race-cultivar specificity. The isolates showed differences in virulence against the cultivars. Three isolates (race 0) caused severe disease only on Woogenellup; 2 isolates (race 1) caused severe disease on Larisa, Trikkala, and Woogenellup, but not on Meteora; one isolate (race 2) caused severe disease on Meteora and Woogenellup, but not on Larisa and Trikkala. As well as differing in virulence (the ability of a race to attack a range of cultivars), the races also differed in their aggressiveness on Woogenellup, with race 2 being the most, and race 0 the least, pathogenic. The isolates varied in their growth rate on agar medium, but this was not related to virulence or aggressiveness.

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