Title |
Macrolides rapidly inhibit red blood cell invasion by the human malaria parasite, Plasmodium falciparum
|
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Published in |
BMC Biology, July 2015
|
DOI | 10.1186/s12915-015-0162-0 |
Pubmed ID | |
Authors |
Danny W Wilson, Christopher D Goodman, Brad E Sleebs, Greta E Weiss, Nienke WM de Jong, Fiona Angrisano, Christine Langer, Jake Baum, Brendan S Crabb, Paul R Gilson, Geoffrey I McFadden, James G Beeson |
Abstract |
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. 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. Safe and effective macrolide antibiotics with dual modalities could be developed to combat malaria and reduce the parasite's options for resistance. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 3 | 20% |
United States | 1 | 7% |
Australia | 1 | 7% |
India | 1 | 7% |
Unknown | 9 | 60% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 14 | 93% |
Scientists | 1 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 2 | 2% |
Germany | 1 | 1% |
Australia | 1 | 1% |
Unknown | 89 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 18 | 19% |
Student > Ph. D. Student | 18 | 19% |
Student > Bachelor | 9 | 10% |
Student > Master | 7 | 8% |
Student > Doctoral Student | 4 | 4% |
Other | 12 | 13% |
Unknown | 25 | 27% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 16 | 17% |
Medicine and Dentistry | 13 | 14% |
Biochemistry, Genetics and Molecular Biology | 9 | 10% |
Chemistry | 9 | 10% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 6% |
Other | 9 | 10% |
Unknown | 31 | 33% |