TY  - JOUR
A1  - Reiling, Sarah J.
A1  - Krohne, Georg
A1  - Friedrich, Oliver
A1  - Geary, Timothy G.
A1  - Rohrbach, Petra
T1  - Chloroquine exposure triggers distinct cellular responses in sensitive versus resistant Plasmodium falciparum parasites
JF  - Scientific Reports
N2  - Chloroquine (CQ) treatment failure in Plasmodium falciparum parasites has been documented for decades, but the pharmacological explanation of this phenotype is not fully understood. Current concepts attribute CQ resistance to reduced accumulation of the drug at a given external CQ concentration ([CQ] ex) in resistant compared to sensitive parasites. The implication of this explanation is that the mechanisms of CQ-induced toxicity in resistant and sensitive strains are similar once lethal internal concentrations have been reached. To test this hypothesis, we investigated the mechanism of CQ-induced toxicity in CQ-sensitive (CQS) versus CQ-resistant (CQR) parasites by analyzing the time-course of cellular responses in these strains after exposure to varying [CQ] ex as determined in 72 h toxicity assays. Parasite killing was delayed in CQR parasites for up to 10 h compared to CQS parasites when exposed to equipotent [CQ] ex. In striking contrast, brief exposure (1 h) to lethal [CQ] ex in CQS but not CQR parasites caused the appearance of hitherto undescribed hemozoin (Hz)-containing compartments in the parasite cytosol. Hz-containing compartments were very rarely observed in CQR parasites even after CQ exposures sufficient to cause irreversible cell death. These findings challenge current concepts that CQ killing of malaria parasites is solely concentration-dependent, and instead suggest that CQS and CQR strains fundamentally differ in the consequences of CQ exposure.
KW  - Cellular imaging
KW  - Parasite development
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225123
VL  - 8
IS  - 11137
ER  - 
TY  - JOUR
A1  - Heil, Hannah S.
A1  - Schreiber, Benjamin
A1  - Götz, Ralph
A1  - Emmerling, Monika
A1  - Dabauvalle, Marie-Christine
A1  - Krohne, Georg
A1  - Höfling, Sven
A1  - Kamp, Martin
A1  - Sauer, Markus
A1  - Heinze, Katrin G.
T1  - Sharpening emitter localization in front of a tuned mirror
JF  - Light: Science & Applications
N2  - Single-molecule localization microscopy (SMLM) aims for maximized precision and a high signal-to-noise ratio1. Both features can be provided by placing the emitter in front of a metal-dielectric nanocoating that acts as a tuned mirror2,3,4. Here, we demonstrate that a higher photon yield at a lower background on biocompatible metal-dielectric nanocoatings substantially improves SMLM performance and increases the localization precision by up to a factor of two. The resolution improvement relies solely on easy-to-fabricate nanocoatings on standard glass coverslips and is spectrally and spatially tunable by the layer design and wavelength, as experimentally demonstrated for dual-color SMLM in cells.
KW  - imaging and sensing
KW  - super-resolution microscopy
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228080
VL  - 7
ER  -