Du Qingyou, Schaap Pauline
College of Life Sciences, University of Dundee, MSI/WTB/JBC complex, Dow Street, Dundee, DD15EH, UK.
College of Life Sciences, University of Dundee, MSI/WTB/JBC complex, Dow Street, Dundee, DD15EH, UK.
Protist. 2014 Sep;165(5):569-79. doi: 10.1016/j.protis.2014.07.003. Epub 2014 Jul 14.
Amoebas and other freely moving protists differentiate into walled cysts when exposed to stress. As cysts, amoeba pathogens are resistant to biocides, preventing treatment and eradication. Lack of gene modification procedures has left the mechanisms of encystation largely unexplored. Genetically tractable Dictyostelium discoideum amoebas require cellulose synthase for formation of multicellular fructifications with cellulose-rich stalk and spore cells. Amoebas of its distant relative Polysphondylium pallidum (Ppal), can additionally encyst individually in response to stress. Ppal has two cellulose synthase genes, DcsA and DcsB, which we deleted individually and in combination. Dcsa- mutants formed fruiting bodies with normal stalks, but their spore and cyst walls lacked cellulose, which obliterated stress-resistance of spores and rendered cysts entirely non-viable. A dcsa-/dcsb- mutant made no walled spores, stalk cells or cysts, although simple fruiting structures were formed with a droplet of amoeboid cells resting on an sheathed column of decaying cells. DcsB is expressed in prestalk and stalk cells, while DcsA is additionally expressed in spores and cysts. We conclude that cellulose is essential for encystation and that cellulose synthase may be a suitable target for drugs to prevent encystation and render amoeba pathogens susceptible to conventional antibiotics.
变形虫和其他自由移动的原生生物在受到压力时会分化成有壁的囊肿。作为囊肿,变形虫病原体对杀菌剂具有抗性,从而阻碍了治疗和根除。由于缺乏基因编辑程序,包囊化的机制在很大程度上尚未得到探索。具有遗传易处理性的盘基网柄菌变形虫形成富含纤维素的柄和孢子细胞的多细胞子实体需要纤维素合酶。其远亲苍白聚孢黏菌(Ppal)的变形虫在受到压力时还能单独形成包囊。Ppal有两个纤维素合酶基因,DcsA和DcsB,我们分别单独和组合删除了它们。Dcsa突变体形成的子实体有正常的柄,但其孢子和囊肿壁缺乏纤维素,这消除了孢子的抗逆性,使囊肿完全无法存活。一个dcsa-/dcsb-突变体没有形成有壁的孢子、柄细胞或囊肿,尽管形成了简单的子实体结构,在由腐烂细胞组成的鞘状柱上有一滴变形虫细胞。DcsB在前柄细胞和柄细胞中表达,而DcsA在孢子和囊肿中也有表达。我们得出结论,纤维素对于包囊化至关重要,纤维素合酶可能是药物预防包囊化并使变形虫病原体对传统抗生素敏感的合适靶点。