Lozoya-Pérez Nancy E, Casas-Flores Sergio, de Almeida José Roberto Fogaça, Martínez-Álvarez José A, López-Ramírez Luz A, Jannuzzi Grasielle Pereira, Trujillo-Esquivel Elías, Estrada-Mata Eine, Almeida Sandro R, Franco Bernardo, Lopes-Bezerra Leila M, Mora-Montes Héctor M
Department of Biology, Division of Exact and Natural Sciences, Universidad de Guanajuato, Guanajuato, Mexico,
Division of Molecular Biology, IPICYT, San Luis Potosí, Mexico.
Infect Drug Resist. 2018 Dec 28;12:67-85. doi: 10.2147/IDR.S185037. eCollection 2019.
is a neglected fungal pathogen for the human being and other mammals. In several fungal systems, Och1 is a Golgi α1,6-mannosyltransferase with a key function in the synthesis of -linked glycans; which are important elements during the host-fungus interplay. The role of in fungal virulence seems to be species-specific, being an essential component for virulence and dispensable during the interaction of with the host.
Here, we silenced and characterized the phenotype of the mutant strains.
The mutant strains did not show defects in the cell or colony morphology, the growth rate or the ability to undergo dimorphism; but the cell wall changed in both composition and exposure of inner components at the surface. When interacting with human monocytes, the silenced strains had a reduced ability to stimulate TNFα and IL-6 but stimulated higher levels of IL-10. The interaction with human macrophages was also altered, with reduced numbers of silenced cells phagocytosed. These strains showed virulence attenuation in both and in the mouse model of sporotrichosis. Nonetheless, the cytokine levels in infected organs did not vary significantly when compared with the wild-type strain.
Our data demonstrate that silencing affects different aspects of the -host interaction.
是一种被忽视的人类及其他哺乳动物真菌病原体。在多个真菌系统中,Och1是一种高尔基体α1,6-甘露糖基转移酶,在合成O-连接聚糖中起关键作用;O-连接聚糖是宿主与真菌相互作用过程中的重要元素。在真菌毒力中的作用似乎具有物种特异性,是毒力的重要组成部分,而在与宿主相互作用时并非必需。
在此,我们使沉默并对突变菌株的表型进行了表征。
突变菌株在细胞或菌落形态、生长速率或双态性能力方面未表现出缺陷;但其细胞壁的组成和表面内部成分的暴露发生了变化。与人类单核细胞相互作用时,沉默菌株刺激TNFα和IL-6的能力降低,但刺激IL-10的水平更高。与人类巨噬细胞的相互作用也发生了改变,被吞噬的沉默细胞数量减少。这些菌株在孢子丝菌病的和小鼠模型中均表现出毒力减弱。然而,与野生型菌株相比,感染器官中的细胞因子水平没有显著变化。
我们的数据表明,沉默影响与宿主相互作用的不同方面。