ILANIT 2020

Uncovering a ‘Quorum Sensing-Like’ Mechanism of Malaria Parasites

Anna Rivkin 1 Maria Travin 1 Yaeli Yarkoni 1 Abel C. Camacho 1 Ziv Porat 2 Maxim Itkin 3 Sergey Malitsky 3 Tamar Ziv 4 Nir London 5 Ronen Hazan 6 Zvi Hayouka 7 Moshe Goldsmith 1 Neta Regev-Rudzki 1
1Department of Biomolecular Sciences, Weizmann Institute of Science, Israel
2Flow Cytometry Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Israel
3Life Sciences Core Facilities, Metabolic Profiling Unit, Weizmann Institute of Science, Israel
4Smoler Protein Center, Department of Biology, Technion – Israel Institute of Technology, Israel
5Department of Organic Chemistry, Weizmann Institute of Science, Israel
6Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem, Israel
7Nstitute of Biochemistry, Food Science and Nutrition, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Israel

The ability of pathogens to sense and respond to changes in their host milieu enables them to adapt and survive in hostile environments. In particular, microbes have developed a mechanism called quorum sensing, in which they produce, detect and respond to small, secreted signal molecules. One of the deadliest pathogens in humans is the parasite Plasmodium falciparum (Pf), the infectious agent of the malaria disease, accounting for the death of about half a million people annually. Here, we reveal that these parasites employ a quorum sensing-like mechanism to respond to their own density and coordinate their asexual growth during the blood stage of their life cycle. Namely, Pf parasites govern their own cell density by secreting active molecule(s). Using a combination of biochemical techniques, we chemically characterized the active fraction (autoinducer-like molecule) and revealed it to be a hydrophilic, positively charged molecule of a size ranging from 100Da to 4,000Da. Treating naïve parasites with the active fraction significantly reduces the amount of asexual parasites but has no effect on the development of the sexual forms. Our finding suggests that malaria parasites signal each other to coordinate their asexual growth pattern is a previously unrecognized survival strategy. Identification and further investigation of the active secreted molecule can potentially lead to the development of anti-malaria drugs.









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