Influence of oxygen on asexual blood cycle and susceptibility of Plasmodium falciparum to chloroquine: requirement of a standardized in vitro assay

Briolant, Sébastien; Parola, Philippe; Fusaı̈, Thierry; Madamet-Torrentino, Marilyn; Baret, Eric; Mosnier, Joël; Delmont, J.; Parzy, Daniel; Minodier, Philippe; Rogier, Christophe; Pradines, Bruno

doi:10.1186/1475-2875-6-44

Cited by 35 publications

(46 citation statements)

References 26 publications

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“…This is in agreement with the previous results that showed in 136 P. falciparum fresh isolates from Comoros that the chloroquine IC 50 values at 10% O 2 were significantly higher than those at 21% O 2 , with the means of 173.5 nM and 121.5 nM, respectively [26]. Of particular interest among the 63 isolates that were resistant in vitro to chloroquine (IC 50 >100 nM) at 5% CO 2 and 10% O 2 , was the observation that 17 were susceptible to chloroquine (IC 50 < 100 nM) at 21% O 2 [26]. In the present study, only one of 21 strains with chloroquine IC 50 >100 nM at 10% O 2 had IC 50 < 100 nM at a concentration of 15%.…”

Section: Discussionsupporting

confidence: 93%

Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

Pascual

Basco

Baret

et al. 2011

Malar J

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BackgroundThe aim of this study was to evaluate the cultivation system in which the proper atmospheric conditions for growing Plasmodium falciparum parasites were maintained in a sealed bag. The Genbag® system associated with the atmospheric generators for capnophilic bacteria Genbag CO2® was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions.MethodsThe susceptibility of 36 pre-identified parasite strains from a wide panel of countries was assessed for nine standard anti-malarial drugs (chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone and pyrimethamine) by the standard 42-hour 3H-hypoxanthine uptake inhibition method using the Genbag CO2® system and compared to controlled incubator conditions (5% CO2 and 10% O2).ResultsThe counts per minute values in the control wells in incubator atmospheric conditions (5% CO2 and 10% O2) were significantly higher than those of Genbag® conditions (2738 cpm vs 2282 cpm, p < 0.0001). The geometric mean IC50 estimated under the incubator atmospheric conditions was significantly lower for atovaquone (1.2 vs 2.1 nM, p = 0.0011) and higher for the quinolines: chloroquine (127 vs 94 nM, p < 0.0001), quinine (580 vs 439 nM, p < 0.0001), monodesethylamodiaquine (41.4 vs 31.8 nM, p < 0.0001), mefloquine (57.5 vs 49.7 nM, p = 0.0011) and lumefantrine (23.8 vs 21.2 nM, p = 0.0044). There was no significant difference of IC50 between the 2 conditions for dihydroartemisinin, doxycycline and pyrimethamine.To reduce this difference in term of anti-malarial susceptibility, a specific cut-off was estimated for each drug under Genbag® conditions by regression. The cut-off was estimated at 77 nM for chloroquine (vs 100 nM in 10% O2), 611 nM for quinine (vs 800 nM), 30 nM for mefloquine (vs 30 nM), 61 nM for monodesethylamodiaquine (vs 80 nM) and 1729 nM for pyrimethamine (vs 2000 nM).ConclusionsThe atmospheric generators for capnophilic bacteria Genbag CO2® is an appropriate technology that can be transferred to the field for epidemiological surveys of drug-resistant malaria. The present data suggest the importance of the gas mixture on in vitro microtest results for anti-malarial drugs and the importance of determining the microtest conditions before comparing and analysing the data from different laboratories and concluding on malaria resistance.

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Section: Discussionsupporting

confidence: 93%

Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

Pascual

Basco

Baret

et al. 2011

Malar J

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“…At 48 hours, the second parasitic cycle began for parasites exposed to 5% O 2 (nearly all of them were at ring stage (100%)), while the majority of parasites exposed to 21% O 2 remained in the schizont stage (90% schizonts and 10% ring). Thus, hyperoxia induces a delay of P. falciparum cell cycle of four hours as previously described [23]. After reinvasion during the following cycle (third cycle), hyperoxia exposure did not change parasitaemia and parasites had a normal life cycle without excess lethality (unpublished data).…”

Section: Resultssupporting

confidence: 63%

Global response of Plasmodium falciparum to hyperoxia: a combined transcriptomic and proteomic approach

Torrentino-Madamet

Alméras

Desplans

et al. 2011

Malar J

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BackgroundOver its life cycle, the Plasmodium falciparum parasite is exposed to different environmental conditions, particularly to variations in O2 pressure. For example, the parasite circulates in human venous blood at 5% O2 pressure and in arterial blood, particularly in the lungs, at 13% O2 pressure. Moreover, the parasite is exposed to 21% O2 levels in the salivary glands of mosquitoes.MethodsTo study the metabolic adaptation of P. falciparum to different oxygen pressures during the intraerythrocytic cycle, a combined approach using transcriptomic and proteomic techniques was undertaken.ResultsEven though hyperoxia lengthens the parasitic cycle, significant transcriptional changes were detected in hyperoxic conditions in the late-ring stage. Using PS 6.0™ software (Ariadne Genomics) for microarray analysis, this study demonstrate up-expression of genes involved in antioxidant systems and down-expression of genes involved in the digestive vacuole metabolism and the glycolysis in favour of mitochondrial respiration. Proteomic analysis revealed increased levels of heat shock proteins, and decreased levels of glycolytic enzymes. Some of this regulation reflected post-transcriptional modifications during the hyperoxia response.ConclusionsThese results seem to indicate that hyperoxia activates antioxidant defence systems in parasites to preserve the integrity of its cellular structures. Moreover, environmental constraints seem to induce an energetic metabolism adaptation of P. falciparum. This study provides a better understanding of the adaptive capabilities of P. falciparum to environmental changes and may lead to the development of novel therapeutic targets.

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“…For example, it has been documented that IC 50 values for chloroquine depend highly on the oxygen pressure during the assay. A P. falciparum strain may display chloroquine-resistance (IC 50 >100nM) at 10% O 2 and behave as a sensitive strain at 21% O 2 (Briolant et al, 2007).…”

Section: Interlaboratory Variationsmentioning

confidence: 99%

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

Grellier¹,

Deregnaucourt²,

Isabelle³

2012

Malaria Parasites

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Influence of oxygen on asexual blood cycle and susceptibility of Plasmodium falciparum to chloroquine: requirement of a standardized in vitro assay

Cited by 35 publications

References 26 publications

Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs

Global response of Plasmodium falciparum to hyperoxia: a combined transcriptomic and proteomic approach

Advances in Antimalarial Drug Evaluation and New Targets for Antimalarials

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