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首页> 外文期刊>Infection and immunity >Arginine-Induced Germ Tube Formation in Candida albicans Is Essential for Escape from Murine Macrophage Line RAW 264.7
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Arginine-Induced Germ Tube Formation in Candida albicans Is Essential for Escape from Murine Macrophage Line RAW 264.7

机译:在白色念珠菌中精氨酸诱导的胚芽管形成对于逃离鼠巨噬细胞系RAW 264.7是必不可少的

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The opportunistic fungal pathogen Candida albicans is a part of the normal flora but it also causes systemic candidiasis if it reaches the bloodstream. Upon being phagocytized by macrophages, an important component of innate immunity, C. albicans rapidly upregulates a set of arginine biosynthetic genes. Arginine, urea, and CO2 induced hyphae in a density-dependent manner in wild-type, cph1/cph1, and rim101/rim101 strains but not in efg1/efg1 or cph1/cph1 efg1/efg1 strains. Arginase (Car1p) converts arginine to urea, which in turn is degraded by urea amidolyase (Dur1,2p) to produce CO2, a signal for hyphal switching. We used a dur1,2/dur1,2 mutant (KWN6) and the complemented strain, KWN8 (dur1,2/dur1,2::DUR1,2/DUR1,2) to study germ tube formation. KWN6 could not make germ tubes in the presence of arginine or urea but did in the presence of 5% CO2, which bypasses Dur1,2p. We also tested the effect of arginine on the interaction between the macrophage line RAW 264.7 and several strains of C. albicans. Arginine activated an Efg1p-dependent yeast-to-hypha switch, enabling wild-type C. albicans and KWN8 to escape from macrophages within 6 h, whereas KWN6 was defective in this regard. Additionally, two mutants that cannot synthesize arginine, BWP17 and SN152, were defective in making hyphae inside the macrophages, whereas the corresponding arginine prototrophs, DAY286 and SN87, formed germ tubes and escaped from macrophages. Therefore, metabolism of arginine by C. albicans controls hyphal switching and provides an important mechanism for escaping host defense.
机译:机会性真菌病原体白色念珠菌是正常菌群的一部分,但如果到达血液,也会引起全身性念珠菌病。被巨噬细胞吞噬后,巨噬细胞是先天免疫的重要组成部分 C。白色念珠菌迅速上调了一组精氨酸的生物合成基因。精氨酸,尿素和CO 2 在野生型, cph1 / cph1 rim101 / rim101 菌株中以密度依赖性方式诱导菌丝但不是 efg1 / efg1 cph1 / cph1 efg1 / efg1 菌株。精氨酸酶(Car1p)将精氨酸转化为尿素,然后尿素酰胺分解酶(Dur1,2p)将其降解,产生CO 2 ,这是菌丝转换的信号。我们使用了 dur1,2 / dur1,2 突变体(KWN6)和互补菌株KWN8( dur1,2 / dur1,2 :: DUR1,2 / DUR1,2 )来研究生殖管的形成。 KWN6不能在存在精氨酸或尿素的情况下制造胚管,而在存在5%CO 2 (绕过Dur1,2p)的情况下可以制造胚管。我们还测试了精氨酸对巨噬细胞系RAW 264.7与几株 C之间相互作用的影响。白色的。精氨酸激活了Efg1p依赖型的酵母菌到菌丝的开关,从而使野生型 C成为可能。白色念珠菌和KWN8在6小时内从巨噬细胞中逃逸,而KWN6在这方面是有缺陷的。此外,两个不能合成精氨酸的突变体BWP17和SN152在巨噬细胞内部产生菌丝方面存在缺陷,而相应的精氨酸原养菌DAY286和SN87形成了胚芽管并从巨噬细胞中逃脱了。因此,精氨酸通过 C代谢。白色念珠菌控制着菌丝的切换,为逃避宿主防御提供了重要的机制。

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