School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
PLoS One. 2013 Apr 25;8(4):e60723. doi: 10.1371/journal.pone.0060723. Print 2013.
A key step for the survival of the malaria parasite is the release from and subsequent invasion of erythrocytes by the merozoite. Differences in the efficiency of these two linked processes have a direct impact on overall parasite burden in the host and thereby virulence. A number of parasite proteases have recently been shown to play important roles during both merozoite egress as well as merozoite invasion. The rodent malaria parasite Plasmodium yoelii has been extensively used to investigate the mechanisms of parasite virulence in vivo and a number of important proteins have been identified as being key contributors to pathology. Here we have utilized transcriptional comparisons to identify two protease-like SERAs as playing a potential role in virulence. We show that both SERAs are non-essential for blood stage development of the parasite though they provide a subtle but important growth advantage in vivo. In particular SERA2 appears to be an important factor in enabling the parasite to fully utilize the whole age repertoire of circulating erythrocytes. This work for the first time demonstrates the subtle contributions different protease-like SERAs make to provide the parasite with a maximal capacity to successfully maintain an infection in the host.
疟原虫生存的一个关键步骤是裂殖子从红细胞中释放出来，随后侵入红细胞。这两个相互关联的过程的效率差异对宿主体内寄生虫的总负荷，进而对毒力有直接影响。最近发现，一些寄生虫蛋白酶在裂殖子逸出和侵入过程中都发挥着重要作用。鼠疟原虫 Plasmodium yoelii 被广泛用于研究寄生虫在体内的毒力机制，已经确定了一些重要的蛋白质是导致病理学的关键因素。在这里，我们利用转录比较来鉴定两种蛋白酶样 SERAs 可能在毒力中发挥作用。我们表明，尽管这两种 SERAs 对寄生虫的红血细胞发育不是必需的，但它们在体内提供了一个微妙但重要的生长优势。特别是 SERA2 似乎是使寄生虫能够充分利用循环红细胞整个年龄谱的重要因素。这项工作首次证明了不同蛋白酶样 SERAs 对寄生虫提供最大能力以成功维持宿主感染的微妙贡献。
