Molecular genetic mechanisms of drug resistance in Plasmodium falciparum

2020 ◽  
Vol 4_2020 ◽  
pp. 80-87
Author(s):  
Solovyev A.I. Solovyev ◽  
Uskov A.N. Uskov ◽  
Kovalenko A.N. Kovalenko ◽  
Kapatsyna V.A. Kapatsyna ◽  
Rakin A.I. Rakin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Genetic ◽  
Genetic Mechanisms

Molecular genetic mechanisms of drug resistance in Plasmodium falciparum

2020 ◽  
Vol 4_2020 ◽  
pp. 80-87
Author(s):  
Solovyev A.I. Solovyev ◽  
Uskov A.N. Uskov ◽  
Kovalenko A.N. Kovalenko ◽  
Kapatsyna V.A. Kapatsyna ◽  
Rakin A.I. Rakin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Genetic ◽  
Genetic Mechanisms

Molecular genetic mechanisms of drug resistance in Plasmodium falciparum

2020 ◽  
Vol 4_2020 ◽  
pp. 80-87
Author(s):  
Solovyev A.I. Solovyev ◽  
Uskov A.N. Uskov ◽  
Kovalenko A.N. Kovalenko ◽  
Kapatsyna V.A. Kapatsyna ◽  
Rakin A.I. Rakin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Genetic ◽  
Genetic Mechanisms

scholarly journals MOLECULAR-GENETIC MECHANISMS OF PLASMODIUM FALCIPARUM VIRULENCE AND TROPICAL MALARIA PATHOGENESIS

2018 ◽  
Vol 10 (3) ◽  
pp. 23-29
Author(s):  
A. N. Uskov ◽  
A. I. Soloviev ◽  
V. Yu. Kravtsov ◽  
R. V. Gudkov ◽  
E. V. Kolomoets ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Surface ◽  
Complex Structure ◽  
Molecular Genetic ◽  
Regulation Of Gene Expression ◽  
Clinical Malaria ◽  
Tissue Level ◽  
Cellular Level ◽  
Genetic Mechanisms ◽  
Main Factor

There is introduced the analysis of molecular-genetic mechanisms of tropical malaria pathogenesis and P. falciparum virulence. It is shown, that pathogenesis of tropical malaria is associated with the properties of red blood cells membrane surface (RBCs or erythrocytes) that are infected by P. falciparum. There are «knobs structures» on membrane surface infected RBCs. Knobs structures contains a complex of P. falciparum proteins – PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1). PfEMP1 is associated with virulence of P. falciparum. Complex PfEMP1 has difficult polymorphous structure. Domains of PfEMP1 are able to associate with different cell receptors. Virulence`s individual components of the main factor are selectively sensitive to different tissues and organs. The severity of the clinical malaria infection course depends on the complex structure PfEMP1 of malaria parasites. Composition of polypeptide PfEMP1 is determined by var-complex. Nowadays there are 60 variants of var-complex. Regulation of gene expression, forming part of the var-complex, is carried out on a molecular-genetic level, cellular level, tissue level. Modern research in this area are aimed to explore genes polymorphism of the virulence`s main factor, to identify mechanism of its differential expression. Search of molecular – genetic markers is relevant to develop methods of gene diagnostic and malaria vaccine.

Molecular genetic mechanisms of drug resistance in prostate cancer

2015 ◽  
Vol 49 (5) ◽  
pp. 638-648 ◽  
Author(s):  
G. S. Krasnov ◽  
A. A. Dmitriev ◽  
A. F. Sadritdinova ◽  
N. N. Volchenko ◽  
E. N. Slavnova ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Molecular Genetic ◽  
Genetic Mechanisms

scholarly journals Exploration of the Plasmodium falciparum Resistome and Druggable Genome Reveals New Mechanisms of Drug Resistance and Antimalarial Targets

2018 ◽  
Vol 11 ◽  
pp. 117863611880852 ◽  
Author(s):  
Annie Cowell ◽  
Elizabeth Winzeler
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Drug Targets ◽  
Antimalarial Activity ◽  
Genomic Analysis ◽  
Microbial Pathogens ◽  
Antimalarial Resistance ◽  
Genetic Mechanisms ◽  
Human Immune Response

Plasmodium parasites, the causative agent of malaria infections, rapidly evolve drug resistance and escape detection by the human immune response via the incredible mutability of its genome. Understanding the genetic mechanisms by which Plasmodium parasites develop antimalarial resistance is essential to understanding why most drugs fail in the clinic and designing the next generation of therapies. A systematic genomic analysis of 262 Plasmodium falciparum clones with stable in vitro resistance to 37 diverse compounds with potent antimalarial activity was undertaken with the main goal of identifying new drug targets. Despite several challenges inherent to this method of in vitro drug resistance generation followed by whole genome sequencing, the study was able to identify a likely drug target or resistance gene for every compound for which resistant parasites could be generated. Known and novel P falciparum resistance mediators were discovered along with several new promising antimalarial drug targets. Surprisingly, gene amplification events contributed to one-third of the drug resistance acquisition events. The study can serve as a model for drug discovery and resistance analyses in other similar microbial pathogens amenable to in vitro culture.

Gene mutation and drug resistance of M. tuberculosis in the patients followed up in the city of Moscow

2020 ◽  
Vol 97 (12) ◽  
pp. 34-44
Author(s):  
M. A. Krasnova ◽  
E. M. Belilovsky ◽  
S. E. Borisov ◽  
A. A. Khakhalina ◽  
Yu. D. Mikhaylova ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Statistical Significance ◽  
Molecular Genetic ◽  
Previous Treatment ◽  
Repeated Treatment ◽  
Phenotypic Resistance ◽  
Therapy Regimen ◽  
Treatment History ◽  
History Of ◽  
Relationship Of

The article describes a retrospective study of the results of microbiological and molecular genetic tests of 685 M. tuberculosis cultures isolated from 685 adult tuberculosis patients registered for dispensary follow-up in Moscow in 2014.The following was identified during the study: phenotypic drug resistance (FDR) of MTB to rifampicin, isoniazid, fluoroquinolones, kanamycin, amikacin, and capreomycin in groups of patients with different treatment history; the frequency of FDR to the above anti-tuberculosis drugs in strains with mutations being drug resistance markers; the frequency of various mutations in case of FDR of mycobacteria in the patients from different groups; the relationship of FDR or the presence of a particular mutation with various characteristics of the patients and their treatment history.The history of previous treatment was determined as statistical significance to provide the greatest influence on the spread of drug resistant MTB: patients undergoing repeated treatment had FDR more often and also a much more pronounced variety of mutations being markers of FDR to certain anti-tuberculosis drugs.The results of the study showed that the detection of genetic mutations in MBT associated with FDR was a reliable tool for predicting phenotypic resistance and should be used as the main method for selecting anti-tuberculosis drugs when compiling the etiotropic therapy regimen.

scholarly journals Assessment of the Drug Susceptibility of Plasmodium falciparum Clinical Isolates from Africa by Using a Plasmodium Lactate Dehydrogenase Immunodetection Assay and an Inhibitory Maximum Effect Model for Precise Measurement of the 50-Percent Inhibitory Concentration

2006 ◽  
Vol 50 (10) ◽  
pp. 3343-3349 ◽  
Author(s):  
Halima Kaddouri ◽  
Serge Nakache ◽  
Sandrine Houzé ◽  
France Mentré ◽  
Jacques Le Bras
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Active Metabolite ◽  
Inhibitory Concentration ◽  
Drug Susceptibility ◽  
Maximum Effect ◽  
Malaria Parasites ◽  
Effect Model

ABSTRACT The extension of drug resistance among malaria-causing Plasmodium falciparum parasites in Africa necessitates implementation of new combined therapeutic strategies. Drug susceptibility phenotyping requires precise measurements. Until recently, schizont maturation and isotopic in vitro assays were the only methods available, but their use was limited by technical constraints. This explains the revived interest in the development of replacement methods, such as the Plasmodium lactate dehydrogenase (pLDH) immunodetection assay. We evaluated a commercially controlled pLDH enzyme-linked immunosorbent assay (ELISA; the ELISA-Malaria antigen test; DiaMed AG, Cressier s/Morat, Switzerland) to assess drug susceptibility in a standard in vitro assay using fairly basic laboratory equipment to study the in vitro resistance of malaria parasites to major antimalarials. Five Plasmodium falciparum clones and 121 clinical African isolates collected during 2003 and 2004 were studied by the pLDH ELISA and the [8-3H]hypoxanthine isotopic assay as a reference with four antimalarials. Nonlinear regression with a maximum effect model was used to estimate the 50% inhibitory concentration (IC50) and its confidence intervals. The two methods were observed to have similar reproducibilities, but the pLDH ELISA demonstrated a higher sensitivity. The high correlation (r = 0.98) and the high phenotypic agreement (κ = 0.88) between the two methods allowed comparison by determination of the IC50s. Recently collected Plasmodium falciparum African isolates were tested by pLDH ELISA and showed drug resistance or decreased susceptibilities of 62% to chloroquine and 11.5% to the active metabolite of amodiaquine. No decreased susceptibility to lumefantrine or the active metabolite of artemisinin was detected. The availability of this simple and highly sensitive pLDH immunodetection assay will provide an easier method for drug susceptibility testing of malaria parasites.

Detection of Genetic markers associated with Plasmodium falciparum drug resistance among malaria patients in Kaduna State, Nigeria

2021 ◽  
Vol 42 (2) ◽  
pp. 206-213
Author(s):  
G.Y. Benjamin ◽  
H.I. Inabo ◽  
M.H.I. Doko ◽  
B.O. Olayinka
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Phylogenetic Tree ◽  
Genetic Markers ◽  
Cross Sectional Study ◽  
Sub Saharan Africa ◽  
Health Concern ◽  
Cross Sectional ◽  
Blood Samples ◽  
Test Kit

Malaria is a disease of public health concern in Nigeria and sub-Saharan Africa. It is caused by intracellular parasites of the genus Plasmodium. The aim of this study was to detect genetic markers associated with Plasmodium falciparum drug resistance among malaria patients in Kaduna State, Nigeria. The study was a cross-sectional study that lasted from May 2018 to October 2018. Three hundred blood samples were collected from consenting individuals attending selected hospitals, in the three senatorial districts of Kaduna State, Nigeria. Structured questionnaire were used to obtain relevant data from study participants. The blood samples were screened for malaria parasites using microscopy and rapid diagnostic test kit. Polymerase Chain Reaction was used for detection of the drug resistance genes. Pfcrt, pfmdr1, pfdhfr, pfdhps and pfatpase6 genes were detected at expected amplicon sizes from the malaria positive samples. The pfatpase6 PCR amplicons were sequenced and a phylogenetic tree was created to determine their relatedness. Result showed that Pfcrt (80%) had the highest prevalence, followed by pfdhfr (60%), pfmdr1 (36%) and pfdhps (8%). Pfatpase6 was also detected in 73.3% of the samples, and a phylogenetic tree showed relatedness between the pfatpase6  sequences in this study and those deposited in the GenBank. In conclusion, the study detected that Plasmodium falciparum genes were associated with drug resistance to commonly used antimalarials.

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