构成性激活双组件系统揭示了Streptococcus agalactiae中的调节性网络相互作用
Cosme Claverie1, Francesco Coppolino1,2, Maria-Vittoria Mazzuoli1
1Institut Pasteur, Université Paris Cité, Department of Microbiology, Biology of Gram-Positive Pathogens, Paris, France.
Nature communications
|October 25, 2024
概括
无活化细菌胺酶酸酶的活性构成性地激活两个组成系统 (TCSs). 这种方法绘制了细菌调节网络的地图,并揭示了参与宿主相互作用和细胞包膜平衡的新信号通路.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 细菌生理学 细菌生理学
背景情况:
- 细菌的两组分系统 (TCS) 通过基因酶 (HK) 和反应调节器相互作用来调节重要的细胞过程.
- HKs通常具有酸酶活性,该活性会在响应环境线索时禁用TCS信号.
研究的目的:
- 研究HK酸酶活性失活对*Streptococcus agalactiae*中TCS信号传递的影响.
- 建立构成性TCS激活的方法,以映射调节网络并发现生物功能.
主要方法:
- 在14个*S. agalactiae* HK突变体中,系统地禁用保存的HK酸酶活性.
- 对HK突变的转录组分析 (RNA测序) 来评估全球基因表达变化.
- 针对特定的TCS规律 (例如,SaeRS,BceRS) 和蛋白质相互作用的有针对性的分析.
主要成果:
- 失活HK酸酶活性构成性地激活TCS信号,验证酸酶机制在TCS抑制中的作用.
- 对多个TCS的规则的高分辨率映射,揭示了从专业到全球网络的各种监管策略.
- 确定PbsP作为连接SaeRS和CovRS通路的信号分子,对于宿主-病原体相互作用至关重要.
- 构成性BceRS激活表明细胞包膜恒温的作用超出了抗菌素耐药性.
结论:
- 通过缺乏酸酶的HKs来激活构成性TCS是剖析细菌调节网络的通用工具.
- 这种方法揭示了TCS的新信号通路和生物功能,包括在毒性和细胞外维护中的作用.
- 这些发现为细菌适应和宿主相互作用机制提供了更深入的理解.
相关概念视频
Global Regulatory Systems
2
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
2
Gene Regulation in Microbial Communities: Quorum Sensing
3
Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...
3
Bacterial Signaling
31.5K
Bacterial signaling can occur within bacteria (intracellular) or between bacteria (intercellular). At times, a group of bacteria behaves like a community. To achieve this, they engage in quorum sensing, the perception of higher cell density that causes changes in gene expression. Quorum sensing involves both extracellular and intracellular signaling. The signaling cascade starts with a molecule called an autoinducer (AI). Individual bacteria produce AIs that move out of the bacterial cell...
31.5K
Prokaryotic Transcriptional Activators and Repressors
20.8K
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
20.8K
Constitutive and Regulated Gene Expression
1
Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
1
Inducible Operons: lac Operon
9
The lac operon in Escherichia coli is a model for understanding inducible gene regulation and metabolic flexibility. It integrates local control by lactose and global regulation through catabolite repression, enabling E. coli to preferentially metabolize glucose when available and switch to lactose utilization when glucose is scarce.Structure and Function of the lac OperonThe lac operon contains three structural genes: lacZ (β-galactosidase), lacY (lactose permease), and lacA...
9


