Journal article
Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum
DW Wilson, CD Goodman, BE Sleebs, GE Weiss, NWM de Jong, F Angrisano, C Langer, J Baum, BS Crabb, PR Gilson, GI McFadden, JG Beeson
BMC Biology | BMC | Published : 2015
Abstract
© 2015 Wilson et al. Background: Malaria invasion of red blood cells involves multiple parasite-specific targets that are easily accessible to inhibitory compounds, making it an attractive target for antimalarial development. However, no current antimalarial agents act against host cell invasion. Results: Here, we demonstrate that the clinically used macrolide antibiotic azithromycin, which is known to kill human malaria asexual blood-stage parasites by blocking protein synthesis in their apicoplast, is also a rapid inhibitor of red blood cell invasion in human (Plasmodium falciparum) and rodent (P. berghei) malarias. Multiple lines of evidence demonstrate that the action of azithromycin in ..
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Grants
Awarded by Australian Cancer Research Foundation
Funding Acknowledgements
We thank Dr Francisco Javier Gamo and Dr Jose Maria Bueno-Calderon (GlaxoSmithKline, Tres Cantos facility, Spain) for the provision of modified azalides. Prof. Alan Cowman, The Walter & Eliza Hall Institute, for advice and support throughout the study. Human erythrocytes were kindly provided by the Red Cross Blood Bank (Melbourne, Australia). This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council (NHMRC) Independent Medical Research Institutes Infrastructure Support Scheme (IRIISS). Funding for the research came from the NHMRC of Australia (program grant 637406 to BSC, GIM and JGB) and a Career Development Award to JGB; Peter Doherty Australian Biomedical Fellowship to DWW (APP1035715); postgraduate research scholarship to FA (APP1055246), the Australian Research Council (Future Fellowship to JGB (FT0992317); JB (FT100100112)) and the Australian Cancer Research Foundation. JB is currently supported by a new Investigator Award from the Wellcome Trust (100993/Z/13/Z). GIM is a Howard Hughes International Scholar. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no conflict of interest exists.