Spatial distribution of heme species in erythrocytes infected with Plasmodium falciparum by use of resonance Raman imaging and multivariate analysis

The multivariate algorithm hierarchical cluster analysis is applied to sets of resonance Raman spectra collected from human erythrocytes infected with the malaria parasite Plasmodium falciparum. The images obtained yield information about the distribution of hemoglobin and hemozoin (or malaria pigment) within the parasitized cells and about their molecular structure. This method has the advantage of conveying more information than other imaging approaches based on resonance Raman spectroscopy, and it is a promising tool to study the hemozoin formation process and its interaction with antimalarial drugs within unstained, well-preserved parasites.

[1]  J. Vennerstrom,et al.  Haematin (haem) polymerization and its inhibition by quinoline antimalarials , 1997 .

[2]  Max Diem,et al.  Raman and Infrared Microspectral Imaging of Mitotic Cells , 2006, Applied spectroscopy.

[3]  T. Spiro,et al.  Resonance Raman spectra of heme proteins. Effects of oxidation and spin state. , 1974, Journal of the American Chemical Society.

[4]  Jürgen Popp,et al.  In situ localization and structural analysis of the malaria pigment hemozoin. , 2007, The journal of physical chemistry. B.

[5]  D. Sullivan,et al.  Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. , 1997, Annual review of microbiology.

[6]  Don McNaughton,et al.  Resonance Raman spectroscopy in malaria research , 2006, Expert review of proteomics.

[7]  J. H. Ward Hierarchical Grouping to Optimize an Objective Function , 1963 .

[8]  Christoph Krafft,et al.  Studies on stress-induced changes at the subcellular level by Raman microspectroscopic mapping. , 2006, Analytical chemistry.

[9]  Y. Kraan,et al.  Single-cell Raman and fluorescence microscopy reveal the association of lipid bodies with phagosomes in leukocytes. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Schmitt,et al.  In vitro polarization‐resolved resonance Raman studies of the interaction of hematin with the antimalarial drug chloroquine , 2004 .

[11]  Nicholas J White,et al.  Antimalarial drug resistance. , 2004, The Journal of clinical investigation.

[12]  W. Trager,et al.  Human malaria parasites in continuous culture. , 1976, Science.

[13]  T. Egan,et al.  Quinoline anti‐malarial drugs inhibit spontaneous formation of β‐haematin (malaria pigment) , 1994 .

[14]  J. Merlin,et al.  Spectroscopic Investigations of Malaria Pigment , 1993 .

[15]  J. Breman,et al.  Defining and Defeating the Intolerable Burden of Malaria III. Progress and Perspectives , 2007 .

[16]  T. Egan,et al.  Physico-chemical aspects of hemozoin (malaria pigment) structure and formation. , 2002, Journal of inorganic biochemistry.

[17]  H. Charles Romesburg,et al.  Cluster analysis for researchers , 1984 .

[18]  T. Egan,et al.  Haemozoin (β‐haematin) biomineralization occurs by self‐assembly near the lipid/water interface , 2006, FEBS letters.

[19]  Peter W. Stephens,et al.  The structure of malaria pigment β-haematin , 2000, Nature.

[20]  Don McNaughton,et al.  Raman imaging of hemozoin within the food vacuole of Plasmodium falciparum trophozoites , 2003, FEBS letters.

[21]  I. Robinson,et al.  Crystal nucleation, growth, and morphology of the synthetic malaria pigment beta-hematin and the effect thereon by quinoline additives: the malaria pigment as a target of various antimalarial drugs. , 2007, Journal of the American Chemical Society.