Effect of metalloprotease inhibitors on invasion of red blood cell by Plasmodium falciparum

Abstract

For successful invasion, the malaria merozoite needs to attach to the red blood cell membrane, undergo reorientation, form a junction of the apical end with the host membrane, and internalize. Malaria proteases have been implicated in the invasion process, but their specific cellular functions remain unclear. To demonstrate the involvement of metalloprotease in the process of Plasmodium falciparum merozoite entry into host red blood cell, schizont-infected red blood cells and parasitophorous vacuolar membrane-enclosed merozoite structures were treated with 1,10-phenanthroline, a metal chelator, resulting in a reduction of invasion with IC50value of 25 and 29 μM, respectively. Absence of an accumulation of schizont stages after treatment with 1,10-phenanthroline indicated that the inhibitory effect was not due to suppression of merozoite release from red blood cells, but on the invasion step. Although treatment with GM6001, a well-known inhibitor of the mammalian matrix and disintegrin metalloprotease family, was less effective, nevertheless this study points to the importance of metal-requiring protease in the process of invasion of host red blood cell by the malaria parasite. © 2005 Elsevier B.V. All rights reserved.