Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Im Neuenheimer Feld 344, 69120, Heidelberg, Germany.
German Center for Infection Research, Partner Site Heidelberg, 69120, Heidelberg, Germany.
Malar J. 2021 Oct 30;20(1):430. doi: 10.1186/s12936-021-03960-3.
Plasmodium sporozoites are the highly motile forms of malaria-causing parasites that are transmitted by the mosquito to the vertebrate host. Sporozoites need to enter and cross several cellular and tissue barriers for which they employ a set of surface proteins. Three of these proteins are members of the thrombospondin related anonymous protein (TRAP) family. Here, potential additive, synergistic or antagonistic roles of these adhesion proteins were investigated.
Four transgenic Plasmodium berghei parasite lines that lacked two or all three of the TRAP family adhesins TRAP, TLP and TREP were generated using positive-negative selection. The parasite lines were investigated for their capacity to attach to and move on glass, their ability to egress from oocysts and their capacity to enter mosquito salivary glands. One strain was in addition interrogated for its capacity to infect mice.
The major phenotype of the TRAP single gene deletion dominates additional gene deletion phenotypes. All parasite lines including the one lacking all three proteins were able to conduct some form of active, if unproductive movement.
The individual TRAP-family adhesins appear to play functionally distinct roles during motility and infection. Other proteins must contribute to substrate adhesion and gliding motility.
疟原虫的子孢子是具有高度运动性的疟原虫形式,由蚊子传播给脊椎动物宿主。子孢子需要进入并穿过几种细胞和组织屏障,为此它们使用了一组表面蛋白。其中三种蛋白是血栓素相关匿名蛋白 (TRAP) 家族的成员。在这里,研究了这些粘附蛋白的潜在附加、协同或拮抗作用。
使用正-负选择生成了四种缺乏 TRAP 家族黏附素 TRAP、TLP 和 TREP 中的两种或全部三种的转基因伯氏疟原虫寄生虫系。研究了寄生虫系在玻璃上附着和移动的能力、从卵囊逸出的能力以及进入蚊子唾液腺的能力。此外,还对一种菌株的感染老鼠的能力进行了检测。
TRAP 单基因缺失的主要表型主导了其他基因缺失表型。包括缺乏所有三种蛋白的所有寄生虫系都能够进行某种形式的主动运动,即使没有产生效果。
单个 TRAP 家族黏附素在运动和感染过程中似乎发挥着功能不同的作用。其他蛋白必须有助于底物附着和滑行运动。