Genetics, Genomics and Systems Biology, School of BioSciences, University of Melbourne, Victoria, 3010, Australia.
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, 3800, Australia.
Sci Rep. 2021 Jan 27;11(1):2334. doi: 10.1038/s41598-020-79593-4.
Microbial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37 °C) is a key trigger for the dimorphic switch. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces marneffei that controls cell morphology in response to host cues rather than temperature. The msgA gene is upregulated during murine macrophage infection, and deletion results in aberrant yeast morphology solely during growth inside macrophages. MsgA contains a Dbl homology domain, and a Bin, Amphiphysin, Rvs (BAR) domain instead of a Plekstrin homology domain typically associated with guanine nucleotide exchange factors (GEFs). The BAR domain is crucial in maintaining yeast morphology and cellular localisation during infection. The data suggests that MsgA does not act as a canonical GEF during macrophage infection and identifies a temperature independent pathway in T. marneffei that controls intracellular yeast morphogenesis.
微生物病原体进化出许多策略来逃避宿主免疫系统的识别，包括利用吞噬细胞作为增殖的小生境。二相性致病真菌采用诱导形态发生转变，从多细胞菌丝体转变为更适合细胞内生长的单细胞酵母。向哺乳动物宿主体温（37°C）的转变是二相性转变的关键触发因素。本研究描述了来自二相性真菌病原体马尔尼菲青霉的一个新基因 msgA，该基因控制细胞形态对宿主信号的反应，而不是对温度的反应。在鼠巨噬细胞感染过程中，msgA 基因上调，缺失导致仅在巨噬细胞内生长时酵母形态异常。MsgA 含有一个 Dbl 同源结构域和一个 Bin、Amphiphysin、Rvs（BAR）结构域，而不是与鸟嘌呤核苷酸交换因子（GEF）相关的典型 Plekstrin 同源结构域。BAR 结构域对于维持感染过程中的酵母形态和细胞定位至关重要。数据表明，MsgA 在巨噬细胞感染过程中不作为典型的 GEF 发挥作用，并确定了 T. marneffei 中控制细胞内酵母形态发生的一种不依赖于温度的途径。
