Variant merozoite protein expression is associated with erythrocyte invasion phenotypes in Plasmodium falciparum isolates from Tanzania

[No abstract available

Mutations in Transmembrane Domains 1, 4 and 9 of the Plasmodium falciparum Chloroquine Resistance Transporter Alter Susceptibility to Chloroquine, Quinine and Quinidine

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) can result in verapamil-reversible CQ resistance and altered susceptibility to other antimalarials. PfCRT contains 10 membrane-spanning domains and is found in the digestive vacuole (DV) membrane of intraerythrocytic parasites. The mechanism by which PfCRT mediates CQ resistance is unclear although it is associated with decreased accumulation of drug within the DV. On the permissive background of the P. falciparum 106/1(K76) parasite line, we used single-step drug selection to generate isogenic clones containing unique pfcrt point mutations that resulted in amino acid changes in PfCRT transmembrane domains 1 (C72R, K76N, K76I and K76T) and 9 (Q352K, Q352R). The resulting changes of charge and hydropathy affected quantitative CQ susceptibility and accumulation as well as the stereospecific responses to quinine and quinidine. These results, together with a previously described S163R mutation in transmembrane domain 4, indicate that transmembrane segments 1, 4 and 9 of PfCRT provide important structural components of a substrate recognition and translocation domain. Charge-affecting mutations within these segments may affect the ability of PfCRT to bind different quinoline drugs and determine their net accumulation in the DV. © 2006 The Authors Journal compilation © 2006 Blackwell Publishing Lt

Population genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesi

Malaria cases due to the zoonotic parasite P. knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and 5 lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genome-wide nucleotide diversity (π = 6.03 x 10-3) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species P. falciparum and P. vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates, and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates (mean genome-wide FST = 0.21, with 9,293 SNPs having fixed differences of FST = 1.0). This showed marked heterogeneity across the genome, mean FST values of different chromosomes ranging from 0.08 to 0.34, with further significant variation across regions within several chromosomes. Analysis of the largest cluster (Cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genome-wide average Tajima’s D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp gene had the top value of Tajima’s D = 1.57), and scans of haplotype homozygosity implicate several genomic regions to be under recent positive selection

Erratum to Variant merozoite protein expression is associated with erythrocyte invasion phenotypes in Plasmodium falciparum isolates from Tanzania [Mol. Biochem. Parasitol. 149 (2006) 208-215] (DOI:10.1016/j.molbiopara.2007.01.007)

[No abstract available

Keras R-CNN: Library for cell detection in biological images using deep neural networks

10.1186/s12859-020-03635-xBMC Bioinformatics21130