Deep learning image analysis for continuous single-cell imaging of dynamic processes in Plasmodium falciparum-infected erythrocytes.

Journal: Communications biology
PMID:

Abstract

Continuous high-resolution imaging of the disease-mediating blood stages of the human malaria parasite Plasmodium falciparum faces challenges due to photosensitivity, small parasite size, and the anisotropy and large refractive index of host erythrocytes. Previous studies often relied on snapshot galleries from multiple cells, limiting the investigation of dynamic cellular processes. We present a workflow enabling continuous, single-cell monitoring of live parasites throughout the 48-hour intraerythrocytic life cycle with high spatial and temporal resolution. This approach integrates label-free, three-dimensional differential interference contrast and fluorescence imaging using an Airyscan microscope, automated cell segmentation through pre-trained deep-learning algorithms, and 3D rendering for visualization and time-resolved analyses. As a proof of concept, we applied this workflow to study knob-associated histidine-rich protein (KAHRP) export into the erythrocyte compartment and its clustering beneath the plasma membrane. Our methodology opens avenues for in-depth exploration of dynamic cellular processes in malaria parasites, providing a valuable tool for further investigations.

Authors

  • Sophia M Frangos
    Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Infectious Diseases, Parasitology, Im Neuenheimer Feld 324, Heidelberg, Germany.
  • Sebastian Damrich
    Heidelberg University, Interdisciplinary Center for Scientific Computing (IWR), Im Neuenheimer Feld 205, Heidelberg, Germany.
  • Daniele Gueiber
    Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Infectious Diseases, Parasitology, Im Neuenheimer Feld 324, Heidelberg, Germany.
  • Cecilia P Sanchez
    Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Infectious Diseases, Parasitology, Im Neuenheimer Feld 324, Heidelberg, Germany.
  • Philipp Wiedemann
    University of Applied Sciences Mannheim, Institute of Molecular and Cell Biology, Paul-Wittsack-Strasse 10, Mannheim, Germany.
  • Ulrich S Schwarz
    Heidelberg University, BioQuant and Institute for Theoretical Physics, Philosophenweg 19, Heidelberg, Germany.
  • Fred A Hamprecht
    Heidelberg University, HCI, Speyerer Str. 6, D-69115 Heidelberg, Germany. Electronic address: fred.hamprecht@uni-heidelberg.de.
  • Michael Lanzer
    Heidelberg University, Medical Faculty, University Hospital Heidelberg, Center for Infectious Diseases, Parasitology, Im Neuenheimer Feld 324, Heidelberg, Germany. michael.lanzer@med.uni-heidelberg.de.