Molecular epidemiology of malaria in Yaoundé, Cameroon. III. Analysis of chloroquine resistance and point mutations in the multidrug resistance 1 (pfmdr 1) gene of Plasmodium falciparum.

1998 ◽  
Vol 59 (4) ◽  
pp. 577-581 ◽  
Author(s):  
L K Basco ◽  
P Ringwald
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Molecular Epidemiology ◽  
Point Mutations ◽  
Chloroquine Resistance

scholarly journals Genetic Variations Associated with Drug Resistance Markers in Asymptomatic Plasmodium falciparum Infections in Myanmar

Genes ◽  
2019 ◽  
Vol 10 (9) ◽  
pp. 692 ◽  
Author(s):  
Yan Zhao ◽  
Ziling Liu ◽  
Myat Thu Soe ◽  
Lin Wang ◽  
Than Naing Soe ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Point Mutations ◽  
Multidrug Resistant ◽  
Genetic Variations ◽  
Chloroquine Resistance ◽  
Geographically Dispersed ◽  
Resistance Markers ◽  
Asymptomatic Infections

The emergence and spread of drug resistance is a problem hindering malaria elimination in Southeast Asia. In this study, genetic variations in drug resistance markers of Plasmodium falciparum were determined in parasites from asymptomatic populations located in three geographically dispersed townships of Myanmar by PCR and sequencing. Mutations in dihydrofolate reductase (pfdhfr), dihydropteroate synthase (pfdhps), chloroquine resistance transporter (pfcrt), multidrug resistance protein 1 (pfmdr1), multidrug resistance-associated protein 1 (pfmrp1), and Kelch protein 13 (k13) were present in 92.3%, 97.6%, 84.0%, 98.8%, and 68.3% of the parasites, respectively. The pfcrt K76T, pfmdr1 N86Y, pfmdr1 I185K, and pfmrp1 I876V mutations were present in 82.7%, 2.5%, 87.5%, and 59.8% isolates, respectively. The most prevalent haplotypes for pfdhfr, pfdhps, pfcrt and pfmdr1 were 51I/59R/108N/164L, 436A/437G/540E/581A, 74I/75E/76T/220S/271E/326N/356T/371I, and 86N/130E/184Y/185K/1225V, respectively. In addition, 57 isolates had three different point mutations (K191T, F446I, and P574L) and three types of N-terminal insertions (N, NN, NNN) in the k13 gene. In total, 43 distinct haplotypes potentially associated with multidrug resistance were identified. These findings demonstrate a high prevalence of multidrug-resistant P. falciparum in asymptomatic infections from diverse townships in Myanmar, emphasizing the importance of targeting asymptomatic infections to prevent the spread of drug-resistant P. falciparum.

Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa

2006 ◽  
Vol 6 (4) ◽  
pp. 262-268 ◽  
Author(s):  
Carlo Severini ◽  
Michela Menegon ◽  
Anna Rosa Sannella ◽  
Maria Grazia Paglia ◽  
Pasquale Narciso ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Point Mutations ◽  
Chloroquine Resistance

scholarly journals Survey of Plasmodium falciparum multidrug resistance-1 and chloroquine resistance transporter alleles in Haiti

2013 ◽  
Vol 12 (1) ◽  
pp. 426 ◽  
Author(s):  
Maha A ElBadry ◽  
Alexandre Existe ◽  
Yves S Victor ◽  
Gladys Memnon ◽  
Mark Fukuda ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Chloroquine Resistance ◽  
Chloroquine Resistance Transporter

scholarly journals Reversal of Mefloquine and Quinine Resistance in Plasmodium falciparum with NP30

2003 ◽  
Vol 47 (8) ◽  
pp. 2393-2396 ◽  
Author(s):  
Michelle Ciach ◽  
Kathleen Zong ◽  
Kevin C. Kain ◽  
Ian Crandall
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Genetic Analysis ◽  
Resistance Genes ◽  
Mammalian Cells ◽  
Point Mutations ◽  
In Vitro Assays ◽  
Drug Efflux ◽  
P Glycoprotein

ABSTRACT Quinoline resistance in malaria is frequently compared with P-glycoprotein-mediated multidrug resistance (mdr) in mammalian cells. We have previously reported that nonylphenolethoxylates, such as NP30, are potential Plasmodium falciparum P-glycoprotein substrates and drug efflux inhibitors. We used in vitro assays to compare the ability of verapamil and NP30 to sensitize two parasite isolates to four quinolines: chloroquine (CQ), mefloquine (MF), quinine (QN), and quinidine (QD). NP30 was able to sensitize (reversal, >80%) P. falciparum to MF, QN, QD, and, to a lesser extent, CQ. The presence of 2 μM verapamil had no effect on mefloquine resistance; however, the presence of verapamil modulated the activities of QN and QD in a manner parallel to that observed for CQ. Genetic analysis of putative quinoline resistance genes did not suggest an association between known point mutations in pfcrt and pfmdr1 and NP30 sensitization activity. We conclude that the sensitization action of NP30 is distinct both phenotypically and genotypically from that of verapamil.

Transcripts of the multidrug resistance genes in chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum

Parasitology ◽  
1993 ◽  
Vol 106 (2) ◽  
pp. 107-115 ◽  
Author(s):  
R. M. Ekong ◽  
K. J. H. Robson ◽  
D. A. Baker ◽  
D. C. Warhurst
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Copy Number ◽  
Chloroquine Resistance ◽  
Multidrug Resistance Gene ◽  
Genetic Cross ◽  
Multidrug Resistance Genes

SUMMARYHomologues of the mammalian multidrug resistance gene have been identified in isolates and clones of Plasmodium falciparum and designated pfmdr1 and pfmdr2. Mutations in pfmdr1 have been associated with chloroquine resistance but confirmation could not be obtained in a genetic cross. We have examined the copy number and expression of pfmdr1 and pfmdr2 in chloroquine-sensitive and -resistant P. falciparum and have found no relationship between the copy number of either gene and chloroquine resistance. However, a marked correlation was seen between levels of mRNA transcribed for each gene and chloroquine resistance. Two transcripts of pfmdr1 were detected, and in the asexual blood cycle an 8 kb transcript appeared first, followed by the appearance of a 7 kb species.

Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum

Nature ◽  
1990 ◽  
Vol 345 (6272) ◽  
pp. 255-258 ◽  
Author(s):  
S. J. Foote ◽  
D. E. Kyle ◽  
R. K. Martin ◽  
A. M. J. Oduola ◽  
K. Forsyth ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Resistance Gene ◽  
Chloroquine Resistance ◽  
Multidrug Resistance Gene

Amplification of the multidrug resistance gene pfmdr1 in Plasmodium falciparum has arisen as multiple independent events

1991 ◽  
Vol 11 (10) ◽  
pp. 5244-5250
Author(s):  
T Triglia ◽  
S J Foote ◽  
D J Kemp ◽  
A F Cowman
Keyword(s):  
Polymerase Chain Reaction ◽  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Tumor Cells ◽  
Yeast Artificial Chromosome ◽  
Chloroquine Resistance ◽  
Chain Reaction ◽  
Pfmdr1 Gene ◽  
Independent Events ◽  
Polymerase Chain

The multidrug resistance (MDR) phenotype in mammalian tumor cells can involve amplification of mdr genes that results in overexpression of the protein product termed P-glycoprotein. Chloroquine resistance (CQR) in Plasmodium falciparum has similarities with the MDR phenotype in tumor cells, and some isolates of P. falciparum have amplified levels of the pfmdr1 gene. To investigate the nature and origin of pfmdr1 amplicons, we have cloned large regions of a 110-kb amplicon from the CQR cloned isolate B8 by using the yeast artificial chromosome system. We have identified and sequenced the breakpoints of the amplicon by a novel method employing inverted polymerase chain reaction that is applicable to analysis of any large-scale repeat. We show that the five copies of the amplicon in this isolate are in a head to tail configuration. A string of 30 A's flank the breakpoints on each side of the amplified segment, suggesting a mechanism for the origin of the tandem amplification. Polymerase chain reaction analysis with oligonucleotides that cross the B8 breakpoint has shown in 26 independent CQR isolates, 16 of which contain amplified copies of pfmdr1, that amplification of the pfmdr1 gene in P. falciparum has arisen as multiple independent events. These results suggest that this region of the genome is under strong selective pressure.

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