Gene Expression During Sporulation

描述(申请人提供)：本提案重点介绍枯草芽孢杆菌如何形成孢子。枯草芽孢杆菌因其遗传操作简单，已成为研究原核生物孢子形成和细胞分化的范例。枯草杆菌孢子形成的所有关键调节因素也存在于其他孢子形成物种中，包括炭疽杆菌、破伤风杆菌、产气荚膜梭菌、肉毒杆菌和艰难梭菌，它们分别是炭疽、破伤风、气性坏疽、肉毒杆菌中毒和抗生素治疗后结肠炎的原因。高度抗性的孢子对这些物种在自然界中的生存至关重要。对枯草杆菌的研究得出的结论对这些物种具有普遍的有效性。孢子形成包括分裂成两种不同的细胞类型，即母细胞和前孢子。前孢子被母细胞吞噬，发育成成熟孢子。孢子的形成需要四种RNA聚合酶因子的作用，前孢子中有F，然后是G，母细胞中有E和K。它提出了发育生物学的一个基本问题：基因表达如何与形态变化相协调？该提案解决了这个问题。当来自前孢子的激活母细胞内E的信号被延迟时，就采取了一种新的发育途径，即在一个母细胞内形成两个孢子。这一行为开启了有关染色体复制和生长如何在孢子形成过程中被控制的拟议研究。它有助于研究同一种群中基因相同的生物如何遵循不同的发育路径。染色体易位到前孢子后激活？F。建议研究易位的完成如何导致母细胞吞噬前孢子并激活被吞噬的前孢子中的？G。公共卫生相关性：这项建议关注的是枯草杆菌芽胞形成过程中基因表达如何与形态变化相协调的基本问题。在炭疽杆菌、破伤风杆菌、产气荚膜梭菌、肉毒杆菌和艰难梭菌等相关病原菌中也发现了所有关键的产孢子调控基因。重点放在如何改变信号的时间可以改变所采取的发展道路。

DESCRIPTION (provided by applicant): This proposal focuses on how spores are formed by Bacillus subtilis. B. subtilis has become a paradigm for the study of spore formation, and of cell differentiation in prokaryotes, because of the ease of its genetic manipulation. All the key regulators of B. subtilis spore formation are also found in other spore forming species including the pathogens B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile, the causes of anthrax, tetanus, gas gangrene, botulism and colitis following antibiotic therapy, respectively. The highly resistant spores are critical to the survival of theses species in nature. Conclusions from a study of B. subtilis will have general validity for these species. Spore formation involves a characteristic division into two different cell types, the mother cell and the prespore. The prespore is engulfed by the mother cell and develops into the mature spore. Spore formation requires the action of four RNA polymerase factors, ?F and then ?G in the prespore and ?E and then ?K in the mother cell. It presents a fundamental problem of developmental biology: how is gene expression coordinated with morphological change? The proposal addresses this problem. When the ?F-directed signal from the prespore to activate ?E in the mother cell is delayed, a novel developmental path is taken, in which two spores are formed within one mother cell. This behavior opens up the proposed study of how chromosome replication and growth are controlled during sporulation. It facilitates a study of how genetically identical organisms in the same population can follow different developmental paths. Translocation of the chromosome into the prespore follows activation of ?F. It is proposed to study how completion of translocation leads to engulfment of the prespore by the mother cell and activation of ?G in the engulfed prespore. PUBLIC HEALTH RELEVANCE: This proposal focuses on the fundamental problem of how gene expression is coordinated with morphological changes during formation of spores by Bacillus subtilis. All the key sporulation regulatory genes are also found in related pathogens, including B. anthracis, Clostridium tetani, C. perfringens, C. botulinum and C. difficile. Emphasis is placed on how altering the timing of signaling can change the developmental path taken.