Publications & Reports

Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum.

Wilson DW, Goodman CD, Sleebs BE, Weiss GE, de Jong NW, Angrisano F, Langer C, Baum J, Crabb BS, Gilson PR, McFadden GI, Beeson JG
Research Centre for Infectious Diseases, School of Biological Sciences, The University of Adelaide, Adelaide, South Australia. danny.wilson@adelaide.edu.au.

Abstract

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 inhibiting parasite invasion of red blood cells is independent of its inhibition of protein synthesis in the parasite apicoplast, opening up a new strategy to develop a single drug with multiple parasite targets. We identified derivatives of azithromycin and erythromycin that are better invasion inhibitors than parent compounds, offering promise for development of this novel antimalarial strategy. CONCLUSIONS: Safe and effective macrolide antibiotics with dual modalities could be developed to combat malaria and reduce the parasite’s options for resistance.

Project

  • New treatments for malaria
    In response to the need for new anti-malarial drugs to combat drug resistance, identifying and developing novel compounds that inhibit replication of Plasmodium parasites is required.Full details to follow

Publication

  • Journal: BMC Biology
  • Published: 18/07/2015
  • Volume: 13
  • Issue: 1
  • Pagination: 52

Authors

Health Issue

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