Effect of PABA on Chloroquine Resistance in Plasmodium berghei yoelii

Nature ◽  
1972 ◽  
Vol 238 (5359) ◽  
pp. 98-99 ◽  
Author(s):  
RICHARD CARTER
Keyword(s):  
Plasmodium Berghei ◽  
Chloroquine Resistance

Loss of Chloroquine Resistance on Transfer of Plasmodium berghei from Mouse to Hamster

1967 ◽  
Vol 53 (5) ◽  
pp. 1111 ◽  
Author(s):  
William Trager ◽  
Renata Klatt ◽  
Sharon Smith
Keyword(s):  
Plasmodium Berghei ◽  
Chloroquine Resistance

Experimental Induction of Chloroquine Resistance in Plasmodium berghei NK65

2008 ◽  
Vol 3 (1) ◽  
pp. 16-23 ◽  
Author(s):  
A.C. Ene . ◽  
S.E. Atawodi . ◽  
D.A. Ameh . ◽  
H.O. Kwanashie . ◽  
P.U. Agomo .
Keyword(s):  
Plasmodium Berghei ◽  
Chloroquine Resistance ◽  
Experimental Induction

Relations between resistance to chloroquine and acidification of endocytic vesicle of Plasmodium berghei

Parasitology ◽  
1989 ◽  
Vol 98 (1) ◽  
pp. 1-6 ◽  
Author(s):  
J. Mahmalgi ◽  
E. Veignie ◽  
G. Prensier ◽  
S. Moreau
Keyword(s):  
Plasmodium Berghei ◽  
Resistant Strain ◽  
Low Ph ◽  
Chloroquine Resistance ◽  
Acidic Ph ◽  
Endocytic Vesicle ◽  
Complementary Method ◽  
Endocytic Vesicles ◽  
Acidic Compartments

SummaryIn order to visualize low-pH compartments of Plasmodium berghei strains we have used a basic congener of dinitrophenol, 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine (DAMP) which concentrates in acidic compartments, and can be detected by immunocytochemistry with anti-dinitrophenol antibodies. We have demonstrated that in a P. berghei chloroquine-sensitive strain (N strain), DAMP accumulates in the endocytic vacuoles where haemoglobin degradation is occurring. These compartments which have recently been shown to concentrate 4-aminoquinoline drugs (Moreau, Prensier, Maalla & Fortier, 1986) have an acidic pH. Conversely DAMP was found scattered all over the cytoplasm in a P. berghei chloroquine-resistant strain; the same phenomenon was previously observed (Moreau et al. 1986) in the localization of a 4-aminoquinoline on this same strain. Monensin-induced swelling of acidic compartments (Boss & Morre, 1984) was used as a complementary method for the determination of low-pH compartments on P. berghei strains. All the data reported here suggest that chloroquine resistance in P. berghei RC may be related to an impairment in the acidification of endocytic vesicles.

scholarly journals Isolation of Mutants With Reduced Susceptibility to Piperaquine From a Mutator of the Rodent Malaria Parasite Plasmodium berghei

2021 ◽  
Vol 11 ◽  
Author(s):  
Mie Ikeda ◽  
Makoto Hirai ◽  
Shin-Ichiro Tachibana ◽  
Toshiyuki Mori ◽  
Toshihiro Mita
Keyword(s):  
Drug Resistance ◽  
Plasmodium Berghei ◽  
Gene Mutations ◽  
Chloroquine Resistance ◽  
Whole Genome Sequence ◽  
Base Substitution ◽  
Wild Type ◽  
Gene Encoding ◽  
Genetic Changes ◽  
Genetic Tool

Elucidation of the mechanisms of drug resistance in malaria parasites is crucial for combatting the emergence and spread of resistant parasites, which can be achieved by tracing resistance-associated mutations and providing useful information for drug development. Previously, we produced a novel genetic tool, a Plasmodium berghei mutator (PbMut), whose base substitution rate is 36.5 times higher than that of wild-type parasites. Here, we report the isolation of a mutant with reduced susceptibility to piperaquine (PPQ) from PbMut under PPQ pressure by sequential nine-cycle screening and named it PbMut-PPQ-R-P9. The ED50 of PbMut-PPQ-R-P9 was 1.79 times higher than that of wild-type parasites, suggesting that its PPQ resistance is weak. In the 1st screen, recrudescence occurred in the mice infected with PbMut but not in those infected with wild-type parasites, suggesting earlier emergence of PPQ-resistant parasites from PbMut. Whole-genome sequence analysis of PbMut-PPQ-R-P9 clones revealed that eight nonsynonymous mutations were conserved in all clones, including N331I in PbCRT, the gene encoding chloroquine resistance transporter (CRT). The PbCRT(N331I) mutation already existed in the parasite population after the 2nd screen and was predominant in the population after the 8th screen. An artificially inserted PbCRT(N331I) mutation gave rise to reduced PPQ susceptibility in genome-edited parasites (PbCRT-N331I). The PPQ susceptibility and growth rates of PbCRT-N331I parasites were significantly lower than those of PbMut-PPQ-R-P9, implying that additional mutations in the PbMut-PPQ-R9 parasites could compensate for the fitness cost of the PbCRT(N331I) mutation and contribute to reduced PPQ susceptibility. In summary, PbMut could serve as a novel genetic tool for predicting gene mutations responsible for drug resistance. Further study on PbMut-PPQ-R-P9 could identify genetic changes that compensate for fitness costs owing to drug resistance acquisition.

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