Instituto de Bioquímica Médica Leopoldo De Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Instituto Nacional de Ciência e Tecnologia em Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Front Cell Infect Microbiol. 2021 Apr 22;11:633146. doi: 10.3389/fcimb.2021.633146. eCollection 2021.
In the lifecycle, the motile promastigote form is transmitted from the sand fly vector to a mammalian host during a blood meal. Inside vertebrate host macrophages, the parasites can differentiate into the amastigote form and multiply, causing leishmaniasis, one of the most significant neglected tropical diseases. parasites face different conditions throughout their development inside sand flies. Once in the mammalian host, the parasites have to overcome the microbicide repertoire of the cells of the immune system to successfully establish the infection. In this context, the expression of protein phosphatases is of particular interest. Several members of the serine/threonine-specific protein phosphatase (STP), protein tyrosine phosphatase (PTP), and histidine acid phosphatase (HAcP) families have been described in different species. Although their physiological roles have not been fully elucidated, many studies suggest they have an involvement with parasite biology and pathogeny. Phosphatases play a role in adaptation to nutrient starvation during parasite passage through the sand fly midgut. They are also important to parasite virulence, mainly due to the modulation of host cytokine production and impairment of the microbiocidal potential of macrophages. Furthermore, recent whole-genome expression analyses have shown that different phosphatases are upregulated in metacyclic promastigotes, the infective form of the mammalian host. phosphatases are also upregulated in drug-resistant strains, probably due to the increase in drug efflux related to the activation of ABC transporters. Throughout this review, we will describe the physiological roles that have been attributed to endogenous phosphatases, including their involvement in the adaptation, survival, and proliferation of the parasites inside their hosts.
在生命周期中，在吸血期间，运动的前鞭毛体形式从沙蝇传播媒介传播到哺乳动物宿主。在脊椎动物宿主巨噬细胞内，寄生虫可以分化为无鞭毛体形式并繁殖，导致利什曼病，这是最严重的被忽视热带病之一。寄生虫在沙蝇体内发育过程中面临着不同的条件。一旦进入哺乳动物宿主，寄生虫必须克服免疫系统细胞的杀菌剂库，才能成功建立感染。在这种情况下，蛋白磷酸酶的表达特别有趣。已经在不同物种中描述了丝氨酸/苏氨酸特异性蛋白磷酸酶 (STP)、蛋白酪氨酸磷酸酶 (PTP) 和组氨酸酸性磷酸酶 (HAcP) 家族的几个成员。尽管它们的生理作用尚未完全阐明，但许多研究表明它们与寄生虫生物学和病原体有关。磷酸酶在寄生虫通过沙蝇中肠时对营养饥饿的适应中起作用。它们对寄生虫的毒力也很重要，主要是由于调节宿主细胞因子的产生和损害巨噬细胞的杀菌潜力。此外，最近的全基因组表达分析表明，不同的磷酸酶在循环前鞭毛体中上调，循环前鞭毛体是感染哺乳动物宿主的形式。在耐药株中，磷酸酶也上调，可能是由于 ABC 转运蛋白的激活导致药物外排增加所致。在整篇综述中，我们将描述已归因于内源性磷酸酶的生理作用，包括它们在寄生虫在宿主体内的适应、存活和增殖中的参与。
