调节系统的组合作用产生素异阻力
Jacob E Choby1,2,3, Emily K Crispell1,2,3, Muqing Ma1,4
1Emory Antibiotic Resistance Center, Atlanta, GA, USA.
bioRxiv : the preprint server for biology
|August 20, 2025
概括
一个西格玛因子, σE,在Enterobactercloacae种群中产生胆固醇抗性的异质性. 这种异质性与PhoPQ系统活性相结合,对于抗生素的生存至关重要.
科学领域:
- 微生物学
- 遗传学
- 分子生物学
背景情况:
- 不同抗性包括一个更大的易受性子群体中的一个小的抗性子群体.
- 在Enterobacter cloacae中,素异阻力是一个重要的临床挑战.
- 产生胆固醇抗性的表型异质性的机制尚不清楚.
研究的目的:
- 确定产生素耐药性的分子机制.
- 阐明Enterobactercloacae中异质性和耐药性机制之间的相互作用.
主要方法:
- 使用基于转子体的突变发生屏幕来识别参与胆固醇抗异质性的基因.
- 采用单细胞追踪实验来观察素暴露下的种群动态.
- 研究了PhoPQ双组件系统与已识别的异质性因素的作用.
主要成果:
- 确定了西格玛因子 σE 作为抗素异质性的关键发生器.
- 在基线时, σE 在一个小小的亚群中 (1%) 活跃,而这些细胞在暴露于胆固醇中存活.
- 胆固醇耐药性需要σE介导的异质性和PhoPQ介导的脂质A变异.
结论:
- 胆固醇异阻力源于不同调节系统的协调作用.
- 一个"异质生成器" (σE) 和一个"电阻生成器" (PhoPQ) 都是素异质电阻所必需的.
- 这项研究提出了理解抗生素异阻力的新范式.
相关概念视频
Global Regulatory Systems
71
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...
71
Development of Antibiotic Resistance
197
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
197
Stringent Response in E. coli
50
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
50
Gene Regulation in Microbial Communities: Quorum Sensing
92
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,...
92
Coordination of Gene Expression Processes in Bacteria
143
The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
143
Other Stress Responses in Bacteria
62
Bacteria have global regulatory systems that control several types of stress mechanisms. These include Pho regulon and the heat shock response, which are essential systems for environmental adaptation, such as nutrient limitation and proteotoxic stress. The Pho regulon and the heat shock response exemplify bacterial resilience, enabling rapid adaptation to fluctuating environmental conditions.Pho RegulonBacteria require phosphorus for essential cellular processes, including nucleic acid...
62


