Calcium-dependent permeabilization of erythrocytes by a perforin-like protein during egress of malaria parasites

Swati Garg, Shalini Agarwal, Saravanan Kumar, Syed Shams Yazdani, Chetan E. Chitnis and Shailja Singh ()
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Swati Garg: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB)
Shalini Agarwal: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB)
Saravanan Kumar: Plant Biology: Plant Transformation Group, International Centre for Genetic Engineering and Biotechnology (ICGEB)
Syed Shams Yazdani: Synthetic Biology and Biofuels Group, International Centre for Genetic Engineering and Biotechnology (ICGEB)
Chetan E. Chitnis: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB)
Shailja Singh: Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB)

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract Clinical malaria is associated with proliferation of blood-stage parasites. During the blood stage, Plasmodium parasites invade host red blood cells, multiply, egress and reinvade uninfected red blood cells to continue the life cycle. Here we demonstrate that calcium-dependent permeabilization of host red blood cells is critical for egress of Plasmodium falciparum merozoites. Although perforin-like proteins have been predicted to mediate membrane perforation during egress, the expression, activity and mechanism of action of these proteins have not been demonstrated. Here, we show that two perforin-like proteins, perforin-like protein 1 and perforin-like protein 2, are expressed in the blood stage. Perforin-like protein 1 localizes to the red blood cell membrane and parasitophorous vacuolar membrane in mature schizonts following its Ca2+-dependent discharge from micronemes. Furthermore, perforin-like protein 1 shows Ca2+-dependent permeabilization and membranolytic activities suggesting that it may be one of the effector proteins that mediate Ca2+-dependent membrane perforation during egress.

Date: 2013
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DOI: 10.1038/ncomms2725

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