scholarly journals Comparative Analysis of The Kinomes of Plasmodium Falciparum, Plasmodium Vivax And Their Host Homo Sapiens

2021 ◽  
Author(s):  
Jack Adderley ◽  
Christian Doerig
Keyword(s):  
Plasmodium Falciparum ◽  
Drug Discovery ◽  
Plasmodium Vivax ◽  
Homo Sapiens ◽  
Distinct Species ◽  
Phylogenetic Relation ◽  
Multiple Sequence ◽  
Phylogenetic Comparison ◽  
Human Kinome ◽  
High Level

Abstract Background: Novel antimalarials should be effective across all species of malaria parasites that infect humans, especially the two species that bear the most impact, Plasmodium falciparum and Plasmodium vivax. Protein kinases encoded by pathogens, as well as host kinases required for survival of intracellular pathogens, carry considerable potential as targets for antimalarial intervention 1,2. To date, no comprehensive P. vivax kinome assembly has been conducted; and the P. falciparum kinome, first assembled in 2004, requires an update. The present study, aimed to fill these gaps, utilises a recently published structurally-validated multiple sequence alignment (MSA) of the human kinome 3. This MSA is used as a scaffold to assist the alignment of all protein kinase sequences from P. falciparum and P. vivax, and (where possible) their assignment to specific kinase groups/families.Results: We were able to assign six P. falciparum previously classified as OPK or ‘orphans’ (i.e. with no clear phylogenetic relation to any of the established ePK groups) to one of the aforementioned ePK groups. Direct phylogenetic comparison established that despite an overall high level of similarity between the P. falciparum and P. vivax kinomes, which will help in selecting targets for intervention, there are differences that may underlie the biological specificities of these species. Furthermore, we highlight a number of Plasmodium kinases that have a surprisingly high level of homology with their human counterparts and therefore not well suited as targets for drug discovery.Conclusions: Direct comparison of the kinomes of Homo sapiens, P. falciparum and P. vivax sheds additional light on the previously documented divergence of many P. falciparum and P. vivax kinases from those of their human host. We provide the first direct kinome comparison between the phylogenetically distinct species of P. falciparum and P. vivax, illustrating the key similarities and differences which must be considered in the context of kinase-directed antimalarial drug discovery, and discuss the divergences and similarities between the human and Plasmodium kinomes to inform future searches for selective antimalarial intervention.

scholarly journals Phylogenetic Analysis of Phenylalanine Hydroxylase Enzyme and Its Future Aspect in Treatment of Phenylalanine Hydroxylase Enzyme Deficiency (Phenylketonuria)

2020 ◽  
Vol 5 (7) ◽  
pp. 569-572
Author(s):  
Samran Shahid
Keyword(s):  
Phenylalanine Hydroxylase ◽  
Homo Sapiens ◽  
Genetic Mutation ◽  
The Body ◽  
Enzyme Deficiency ◽  
Phylogenetic Relation ◽  
Multiple Sequence ◽  
Future Aspect ◽  
Bioinformatics Databases ◽  
Pah Gene

PAH enzyme is one of the most vital enzymes in protein metabolism of the body. The enzyme has been found in various organisms and thus proves it has evolved along with speciation.PAH catalyses hydroxylation of the aromatic side of the phenylalanine to generate Tyrosine (4-hydroxyphenylalanine), one of the 20 standard amino acids that exist. The buildup of excess phenylalanine in the body due to deficiency of PAH causes a condition called Phenylketonuria which causes significant nerve damage. The condition Phenylketonuria is caused due to genetic mutation in PAH gene (Cr.12 )in an individual which can cause PAH enzyme deficiency. The purpose of this analysis was to use the existing Bioinformatics databases to draw relevant similarities of PAH of Homo sapiens and other organism using BLAST , MSA(Multiple Sequence Alignment) and phylogenetic relation while proposing the use of gene therapy using the data derived to cure Phenylketonuria

scholarly journals THE CULTIVATION OF MALARIAL PLASMODIA (PLASMODIUM VIVAX AND PLASMODIUM FALCIPARUM) IN VITRO

1912 ◽  
Vol 16 (4) ◽  
pp. 567-579 ◽  
Author(s):  
C. C. Bass ◽  
Foster M. Johns
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Plasmodium Vivax ◽  
Blood Cells ◽  
Distinct Species ◽  
Sexual Cycle ◽  
Successive Generations ◽  
Asexual Cycle

The asexual cycle of Plasmodium vivax and Plasmodium falciparum has been cultivated in vitro in human blood. The parasites have been grown also in red blood cells in the presence of Locke's solution, free of calcium chlorid and in the presence of ascitic fluid. The parasites grow within red blood cells and there is no evidence that they can be grown outside of these cells. The parasites are destroyed in a very few minutes in vitro by normal human serum or by all modifications of serum that we have tested. This fact, together with numerous observations of parasites in all stages of growth apparently within red cells, renders untenable the idea of extracorpuscular development. Leucocytes phagocytize and destroy malarial plasmodia growing in vitro only when the parasites escape from their red blood cell capsule or when the latter is perforated or becomes permeable. Successive generations of Plasmodium vivax and Plasmodium falciparum have been cultivated in vitro by removing the leucocytes from the culture and by transplanting to fresh red blood cells and serum at proper intervals. The asexual cycle of Plasmodium vivax and Plasmodium falciparum cultivated in vitro does not differ from the same cycle growing in vivo. The sexual cycle has not been cultivated, though we have obtained some evidence of the possibility of its accomplishment. There can no longer be any doubt that Plasmodium vivax and Plasmodium falciparum are separate and distinct species. When grown in an identical culture medium and under exactly the same conditions they remain distinct. In twenty-nine cultures of æstivo-autumnal parasites many forms and sizes have been observed, so that evidence is supplied of the occurrence of different varieties of ætivo-autumnal malarial plasmodia. The so called tertian ætivo-autumnal variety may be seen at the proper stage in all cultures grown from merozoites. The form and appearance of the same culture of plasmodia may vary greatly under different conditions which are not necessarily destructive to the parasites. Their generation period may vary from thirty hours (ætivo-autumnal) to four days (tertian), as a result of variation in the temperature at which they were cultivated. Sexual parasites grow in the cultures and are more resistant to unfavorable conditions than schizonts, often living several days after the latter die out. Forms suggesting parthenogenesis have been observed.

scholarly journals Widespread zoophagy and detection of Plasmodium spp. in Anopheles mosquitoes in southeastern Madagascar

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Micaela Finney ◽  
Benjamin A. McKenzie ◽  
Bernadette Rabaovola ◽  
Alice Sutcliffe ◽  
Ellen Dotson ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Vector Control ◽  
Plasmodium Vivax ◽  
Malaria Control ◽  
Feeding Behaviour ◽  
Enzyme Linked Immunosorbent Assay ◽  
Habitat Gradient ◽  
Blood Meals ◽  
Feeding Behaviours ◽  
Southeastern Madagascar

Abstract Background Malaria is a top cause of mortality on the island nation of Madagascar, where many rural communities rely on subsistence agriculture and livestock production. Understanding feeding behaviours of Anopheles in this landscape is crucial for optimizing malaria control and prevention strategies. Previous studies in southeastern Madagascar have shown that Anopheles mosquitoes are more frequently captured within 50 m of livestock. However, it remains unknown whether these mosquitoes preferentially feed on livestock. Here, mosquito blood meal sources and Plasmodium sporozoite rates were determined to evaluate patterns of feeding behaviour in Anopheles spp. and malaria transmission in southeastern Madagascar. Methods Across a habitat gradient in southeastern Madagascar 7762 female Anopheles spp. mosquitoes were collected. Of the captured mosquitoes, 492 were visibly blood fed and morphologically identifiable, and a direct enzyme-linked immunosorbent assay (ELISA) was used to test for swine, cattle, chicken, human, and dog blood among these specimens. Host species identification was confirmed for multiple blood meals using PCR along with Sanger sequencing. Additionally, 1,607 Anopheles spp. were screened for the presence of Plasmodium falciparum, P. vivax-210, and P. vivax 247 circumsporozoites (cs) by ELISA. Results Cattle and swine accounted, respectively, for 51% and 41% of all blood meals, with the remaining 8% split between domesticated animals and humans. Of the 1,607 Anopheles spp. screened for Plasmodium falciparum, Plasmodium vivax 210, and Plasmodium vivax 247 cs-protein, 45 tested positive, the most prevalent being P. vivax 247, followed by P. vivax 210 and P. falciparum. Both variants of P. vivax were observed in secondary vectors, including Anopheles squamosus/cydippis, Anopheles coustani, and unknown Anopheles spp. Furthermore, evidence of coinfection of P. falciparum and P. vivax 210 in Anopheles gambiae sensu lato (s.l.) was found. Conclusions Here, feeding behaviour of Anopheles spp. mosquitoes in southeastern Madagascar was evaluated, in a livestock rich landscape. These findings suggest largely zoophagic feeding behaviors of Anopheles spp., including An. gambiae s.l. and presence of both P. vivax and P. falciparum sporozoites in Anopheles spp. A discordance between P. vivax reports in mosquitoes and humans exists, suggesting high prevalence of P. vivax circulating in vectors in the ecosystem despite low reports of clinical vivax malaria in humans in Madagascar. Vector surveillance of P. vivax may be relevant to malaria control and elimination efforts in Madagascar. At present, the high proportion of livestock blood meals in Madagascar may play a role in buffering (zooprophylaxis) or amplifying (zoopotentiation) the impacts of malaria. With malaria vector control efforts focused on indoor feeding behaviours, complementary approaches, such as endectocide-aided vector control in livestock may be an effective strategy for malaria reduction in Madagascar.

scholarly journals The epidemiology and detectability of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in low, moderate and high transmission settings in Ethiopia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Elifaged Hailemeskel ◽  
Surafel K Tebeje ◽  
Sinknesh W. Behaksra ◽  
Girma Shumie ◽  
Getasew Shitaye ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Age Groups ◽  
Diagnostic Tools ◽  
Asymptomatic Malaria ◽  
Rapid Diagnostics ◽  
Cross Sectional ◽  
Low Transmission ◽  
High Transmission ◽  
Study Sites

Abstract Background As countries move to malaria elimination, detecting and targeting asymptomatic malaria infections might be needed. Here, the epidemiology and detectability of asymptomatic Plasmodium falciparum and Plasmodium vivax infections were investigated in different transmission settings in Ethiopia. Method: A total of 1093 dried blood spot (DBS) samples were collected from afebrile and apparently healthy individuals across ten study sites in Ethiopia from 2016 to 2020. Of these, 862 were from community and 231 from school based cross-sectional surveys. Malaria infection status was determined by microscopy or rapid diagnostics tests (RDT) and 18S rRNA-based nested PCR (nPCR). The annual parasite index (API) was used to classify endemicity as low (API > 0 and < 5), moderate (API ≥ 5 and < 100) and high transmission (API ≥ 100) and detectability of infections was assessed in these settings. Results In community surveys, the overall prevalence of asymptomatic Plasmodium infections by microscopy/RDT, nPCR and all methods combined was 12.2% (105/860), 21.6% (183/846) and 24.1% (208/862), respectively. The proportion of nPCR positive infections that was detectable by microscopy/RDT was 48.7% (73/150) for P. falciparum and 4.6% (2/44) for P. vivax. Compared to low transmission settings, the likelihood of detecting infections by microscopy/RDT was increased in moderate (Adjusted odds ratio [AOR]: 3.4; 95% confidence interval [95% CI] 1.6–7.2, P = 0.002) and high endemic settings (AOR = 5.1; 95% CI 2.6–9.9, P < 0.001). After adjustment for site and correlation between observations from the same survey, the likelihood of detecting asymptomatic infections by microscopy/RDT (AOR per year increase = 0.95, 95% CI 0.9–1.0, P = 0.013) declined with age. Conclusions Conventional diagnostics missed nearly half of the asymptomatic Plasmodium reservoir detected by nPCR. The detectability of infections was particularly low in older age groups and low transmission settings. These findings highlight the need for sensitive diagnostic tools to detect the entire parasite reservoir and potential infection transmitters.

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