无性孢子是真菌分散到新生态位的主要载体。欧洲曲霉菌构巢曲霉是研究无性发育的遗传/分子控制的主要参考。在这个物种中,Flb蛋白控制主基因brlA的表达,因此,flb(上游发育激活[UDA])基因中的功能丧失突变阻断brlA转录,因此,分生孢子的生产,带有无性孢子的结构称为分生孢子。然而,特定Flb突变体的杂种表型,例如ΔflbB菌株,在盐胁迫条件下恢复。以前,我们产生了ΔflbB的第二位点突变体的集合,这些突变体无法在补充有NaH2PO4(0.65M)的培养基上分生孢子。这里,我们鉴定了flpA中的Gly347Stop突变是FLIP57表型的原因,并鉴定了异形芽孢杆菌和烟曲霉中假定的细胞周期蛋白FlpA和C末端结构域激酶-1(CTDK-1)复合物的其余假定组分的作用.FlpA,Stk47和FlpB是及时发芽所必需的(I),(ii)在分生孢子发育过程中,从甲虫到phialides(产生分生孢子的细胞)的过渡,和(iii)在A.nidulans中发育性结构(cleistothecia)。这三种蛋白质是细胞核的,Stk47的核质定位取决于FlpA的活性,这与下拉测定中FlpA对Stk47的保留相关。总的来说,这项工作将曲霉菌的假定CTDK-1复合物与生长和发育控制联系起来。鉴定flpA中的突变作为Nidulans中分生孢子的抑制剂和FlpA的功能表征,Stk47和FlpB是形虫和烟曲霉中C末端结构域激酶复合物CTDK-1的推定成员。重要的烟曲霉已被世界卫生组织列入真菌病原体的优先名单,因为(i)它导致90%的侵袭性曲霉病病例,死亡率很高,和(ii)感染对唑类抗真菌剂的耐药性越来越强。Nidulans是一种机会性病原体和腐生菌,在过去的80年中一直用作丝状真菌的参考系统。这里,我们描述了两种曲霉中推定的转录细胞周期蛋白/激酶复合物CTDK-1在形态发生和发育中的作用。相应基因的无效突变体显示出延迟的发芽,异常分生孢子发育,和抑制cleistothecia产生。虽然在高等真核生物中,这种复合物仅由细胞周期蛋白和激酶形成,真菌复合物将包含真菌特异性第三成分,FlpB,这将使激酶(Stk47)和细胞周期蛋白(FlpA)之间的相互作用成为可能,并且可以用作抗真菌剂的靶标。
OBJECTIVE: Aspergillus fumigatus has been included by the World Health Organization in the priority list of fungal pathogens because (i) it causes 90% of invasive aspergillosis cases, with a high mortality rate, and (ii) infections are becoming increasingly resistant to azole antifungals. A. nidulans is an opportunistic pathogen and a saprotroph which has served during the last 80 years as a reference system for filamentous fungi. Here, we characterized the role in morphogenesis and development of the putative transcriptional
cyclin/kinase complex CTDK-1 in both aspergilli. The null mutants of the corresponding genes showed delayed germination, aberrant conidiophore development, and inhibition of cleistothecia production. While in higher eukaryotes this complex is formed only by a
cyclin and a kinase, the fungal complex would incorporate a fungal-specific third component, FlpB, which would enable the interaction between the kinase (Stk47) and the
cyclin (FlpA) and may be used as a target for antifungals.