The two-component histidine kinases DrkA and SlnA are required for in vivo growth in the human pathogen Penicillium marneffei
The two-component histidine kinases DrkA and SlnA are required for in vivo growth in the human pathogen Penicillium marneffei
复制标题
DOI：
10.1111/j.1365-2958.2011.07878.x
复制
发表时间：
2011-12-01
影响因子：
3.6
通讯作者：
Andrianopoulos, Alex
中科院分区：
文献类型：
--
作者：
Boyce, Kylie J.;Schreider, Lena;Andrianopoulos, Alex
为了引起疾病，真菌病原体必须能够逃避或耐受宿主免疫防御系统。一种常用的逃避机制是能够持续驻留在先天免疫系统的巨噬细胞内并在随后的吞噬细胞破坏中幸存下来。为了发生细胞内生长，通常在环境中以丝状菌丝形式生长的真菌病原体必须能够在称为二态性转换的过程中将生长转换为单细胞酵母生长形式。进行二态性转换的提示依赖于对细胞内宿主环境的识别和响应。真核生物利用双组分信号系统来感知和响应外部环境的变化。本研究研究了由 drkA 和 slnA 编码的杂合组氨酸激酶成分在二态性病原体马尔尼菲青霉中的作用。 SlnA 和 DrkA 都是应激适应所必需的，但对于无性发育、菌丝形态发生和细胞壁完整性的不同方面都是独特需要的。重要的是，slnA和drkA对于体内酵母细胞的产生都是必需的，其中slnA是分生孢子萌发所需的，而drkA是巨噬细胞感染期间二态性转换所需的。
In order to cause disease fungal pathogens must be capable of evading or tolerating the host immune defence system. One commonly utilized evasion mechanism is the ability to continually reside within macrophages of the innate immune system and survive subsequent phagocytic destruction. For intracellular growth to occur, fungal pathogens which typically grow in a filamentous hyphal form in the environment must be able to switch growth to a unicellular yeast growth form in a process known as dimorphic switching. The cue to undergo dimorphic switching relies on the recognition of, and response to, the intracellular host environment. Two-component signalling systems are utilized by eukaryotes to sense and respond to changes in the external environment. This study has investigated the role of the hybrid histidine kinase components encoded by drkA and slnA, in the dimorphic pathogen Penicillium marneffei. Both SlnA and DrkA are required for stress adaptation but are uniquely required for different aspects of asexual development, hyphal morphogenesis and cell wall integrity. Importantly, slnA and drkA are both essential for the generation of yeast cells in vivo, with slnA required for the germination of conidia and drkA required for dimorphic switching during macrophage infection.