Aspergillus fumigatus is a major cause of human disease. The survival of this fungus is dependent on the cell wall organization and function of its components. The cell wall integrity pathway (CWIP) is the primary signaling cascade that controls de novo synthesis of the cell wall in fungi. Abundant conidiation is a hallmark in A. fumigatus, and uptake of conidia by a susceptible host is usually the initial event in infection. The formation of conidia is mediated by the development of fungus-specific specialized structures, conidiophores, which are accompanied by cell wall remodeling. The molecular regulation of these changes in cell wall composition required for the rise of conidiophore from the solid surface and to disperse the conidia into the air is currently unknown. Here, we investigated the role of CWIP in conidiation. We show that CWIP pkcA^G579R, mpkA, and rlmA mutants displayed reduced conidiation during synchronized asexual differentiation. The transcription factor RlmA directly regulated the expression of regulators of conidiation, including flbB, flbC, brlA, abaA, and rasB, as well as genes involved in cell wall synthesis and remodeling, and this affected the chitin content in aerial hyphae. Phosphorylation of RlmA and MpkA was increased during asexual differentiation. We also observed that MpkA physically associated with the proteins FlbB, FlbC, BrlA, and RasB during this process, suggesting another level of cross talk between the CWIP and asexual development pathways. In summary, our results support the conclusion that one function of the CWIP is the regulation of asexual development in filamentous fungi.

IMPORTANCE A remarkable feature of the human pathogen Aspergillus fumigatus is its ability to produce impressive amounts of infectious propagules known as conidia. These particles reach immunocompromised patients and may initiate a life-threatening mycosis. The conidiation process in Aspergillus is governed by a sequence of proteins that coordinate the development of conidiophores. This process requires the remodeling of the cell wall so that the conidiophores can rise and withstand the chains of conidia. The events regulating cell wall remodeling during conidiation are currently unknown. Here, we show that the cell wall integrity pathway (CWIP) components RlmA and MpkA directly contribute to the activation of the conidiation cascade by enabling transcription or phosphorylation of critical proteins involved in asexual development. This study points to an essential role for the CWIP during conidiation and provides further insights into the complex regulation of asexual development in filamentous fungi.

烟曲霉是人类疾病的主要原因。这种真菌的存活取决于细胞壁的组织及其成分的功能。细胞壁完整性途径（CWIP）是控制真菌中细胞壁从头合成的主要信号传导级联。丰富的分娩是烟曲霉的标志，易感宿主吸收分生孢子通常是感染的最初事件。分生孢子的形成是由真菌特异性的特殊结构，分生孢子的形成介导的，伴随着细胞壁的重塑。目前尚不清楚从固体表面升起分生孢子并将分生孢子散布到空气中所需的细胞壁组成变化的分子调控。在这里，我们调查了CWIP在整合中的作用。我们显示CWIP pkcA ^G579R，mpkA和rlmA突变体在同步无性分化过程中显示出降低的分生。转录因子RlmA直接调节分生调节子，包括flbB的表达，flbC，brlA，abaA和rasB以及参与细胞壁合成和重塑的基因，这影响了气生菌丝中甲壳质的含量。在无性分化过程中，RlmA和MpkA的磷酸化增加。我们还观察到，在此过程中，MpkA与蛋白质FlbB，FlbC，BrlA和RasB物理相关，这表明CWIP与无性发育途径之间的相互干扰水平更高。总而言之，我们的结果支持以下结论：CWIP的功能之一是调节丝状真菌无性发育。

重要性人类病原体烟曲霉的显着特征是其能够产生大量令人印象深刻的传染性繁殖体（称为分生孢子）的能力。这些颗粒会到达免疫功能低下的患者，并可能引发威胁生命的真菌病。曲霉的分生过程由协调分生孢子形成的蛋白质序列控制。这个过程需要细胞壁的重塑，以便分生孢子可以上升并承受分生孢子的链。目前尚不清楚在分娩过程中调节细胞壁重塑的事件。在这里，我们显示细胞壁完整性途径（CWIP）组件RlmA和MpkA通过使参与无性发育的关键蛋白转录或磷酸化，直接有助于分生孢子的激活。这项研究指出了CWIP在绝育过程中的重要作用，并为丝状真菌无性发育的复杂调控提供了进一步的见解。