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Splenic retention of Plasmodium falciparum gametocytes to block the transmission of malaria
- Source :
- Antimicrobial Agents and Chemotherapy, Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2015, pp.AAC.05030-14. ⟨10.1128/AAC.05030-14⟩, Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2015, pp.AAC.05030-14. 〈10.1128/AAC.05030-14〉, Antimicrobial Agents and Chemotherapy, 2015, pp.AAC.05030-14. ⟨10.1128/AAC.05030-14⟩
- Publication Year :
- 2015
- Publisher :
- HAL CCSD, 2015.
-
Abstract
- Plasmodium falciparum is transmitted from humans to Anopheles mosquito vectors via the sexual erythrocytic forms termed gametocytes. Erythrocyte filtration through microsphere layers (microsphiltration) had shown that circulating gametocytes are deformable. Compounds reducing gametocyte deformability would induce their splenic clearance, thus removing them from the blood circulation and blocking malaria transmission. The hand-made, single-sample prototype for microsphiltration was miniaturized to a 96-well microtiter plate format, and gametocyte retention in the microsphere filters was quantified by high-content imaging. The stiffening activity of 40 pharmacological compounds was assessed in microtiter plates, using a small molecule (calyculin) as a positive control. The stiffening activity of calyculin was assessed in spleen-mimetic microfluidic chips and in macrophage-depleted mice. Marked mechanical retention (80% to 90%) of mature gametocytes was obtained in microplates following exposure to calyculin at concentrations with no effect on parasite viability. Of the 40 compounds tested, including 20 antimalarials, only 5 endoperoxides significantly increased gametocyte retention (1.5- to 2.5-fold; 24 h of exposure at 1 μM). Mature gametocytes exposed to calyculin accumulated in microfluidic chips and were cleared from the circulation of macrophage-depleted mice as rapidly as heat-stiffened erythrocytes, thus confirming results obtained using the microsphiltration assay. An automated miniaturized approach to select compounds for their gametocyte-stiffening effect has been established. Stiffening induces gametocyte clearance both in vitro and in vivo . Based on physiologically validated tools, this screening cascade can identify novel compounds and uncover new targets to block malaria transmission. Innovative applications in hematology are also envisioned.
- Subjects :
- [ SDV.MP.PAR ] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Erythrocytes
[SDV]Life Sciences [q-bio]
Plasmodium falciparum
Models, Biological
Antimalarials
Automation
Mice
03 medical and health sciences
chemistry.chemical_compound
Microtiter plate
In vivo
parasitic diseases
Image Processing, Computer-Assisted
Gametocyte
Animals
Pharmacology (medical)
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Enzyme Inhibitors
Malaria, Falciparum
Biologic Response Modifiers
Oxazoles
Parasite Egg Count
030304 developmental biology
Pharmacology
0303 health sciences
biology
[ SDV ] Life Sciences [q-bio]
030306 microbiology
Macrophages
Anopheles
Microfluidic Analytical Techniques
Flow Cytometry
biology.organism_classification
Virology
Microspheres
In vitro
3. Good health
Cell biology
Infectious Diseases
chemistry
Erythrocyte Count
Marine Toxins
Marine toxin
Filtration
Spleen
Calyculin
Subjects
Details
- Language :
- English
- ISSN :
- 00664804 and 10986596
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy, Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2015, pp.AAC.05030-14. ⟨10.1128/AAC.05030-14⟩, Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2015, pp.AAC.05030-14. 〈10.1128/AAC.05030-14〉, Antimicrobial Agents and Chemotherapy, 2015, pp.AAC.05030-14. ⟨10.1128/AAC.05030-14⟩
- Accession number :
- edsair.doi.dedup.....d0fb7310f7af8b1de284a46f6e9c7ee8