Tenconi Elodie, Traxler Matthew, Tellatin Déborah, van Wezel Gilles P, Rigali Sébastien
InBioS-Centre for Protein Engineering, Institut de Chimie B6a, University of Liège, B-4000 Liège, Belgium.
Hedera-22, Boulevard du rectorat 27b, B-4000 Liège, Belgium.
Antibiotics (Basel). 2020 Nov 26;9(12):847. doi: 10.3390/antibiotics9120847.
Bioactive natural products are typically secreted by the producer strain. Besides that, this allows the targeting of competitors, also filling a protective role, reducing the chance of self-killing. Surprisingly, DNA-degrading and membrane damaging prodiginines (PdGs) are only produced intracellularly, and are required for the onset of the second round of programmed cell death (PCD) in . In this work, we investigated the influence of PdGs on the timing of the morphological differentiation of . The deletion of the transcriptional activator gene that activates the cluster for PdGs or nutrient-mediated reduction of PdG synthesis both resulted in the precocious appearance of mature spore chains. Transcriptional analysis revealed an accelerated expression of key developmental genes in the null mutant, including for the developmental σ factor BldN which is essential for aerial mycelium formation. In contrast, PdG overproduction due to the enhanced copy number of resulted in a delay or block in sporulation. In addition, confocal fluorescence microscopy revealed that the earliest aerial hyphae do not produce PdGs. This suggests that filaments that eventually differentiate into spore chains and are hence required for survival of the colony, are excluded from the second round of PCD induced by PdGs. We propose that one of the roles of PdGs would be to delay the entrance of into the dormancy state (sporulation) by inducing the leakage of the intracellular content of dying filaments thereby providing nutrients for the survivors.
生物活性天然产物通常由产生菌分泌。除此之外,这还能针对竞争者,同时起到保护作用,降低自我杀伤的几率。令人惊讶的是,DNA降解和膜损伤的灵菌红素(PdGs)仅在细胞内产生,并且是第二轮程序性细胞死亡(PCD)开始所必需的。在这项工作中,我们研究了PdGs对[具体研究对象]形态分化时间的影响。激活PdGs基因簇的转录激活基因的缺失或营养介导的PdG合成减少均导致成熟孢子链过早出现。转录分析显示,[具体研究对象]缺失突变体中关键发育基因的表达加速,包括对气生菌丝体形成至关重要的发育σ因子BldN的[相关基因]。相反,由于[相关基因]拷贝数增加导致的PdG过量产生导致孢子形成延迟或受阻。此外,共聚焦荧光显微镜显示最早的气生菌丝不产生PdGs。这表明最终分化为孢子链并因此是菌落生存所必需的菌丝,被排除在由PdGs诱导的第二轮PCD之外。我们提出PdGs的作用之一是通过诱导死亡菌丝细胞内容物的泄漏来延迟[具体研究对象]进入休眠状态(孢子形成),从而为存活者提供营养。