药物运输和亚细胞积累在大肠杆菌内部的成长阶段贡献
Deepak Kumar1, Anindita Gayen1, Manabendra Chandra1,2
1Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India.
ACS infectious diseases
|August 23, 2024
概括
细菌生长阶段显著影响药物的疗效. 活跃生长的细菌表现出更快的药物运输和积累,与非生长细胞不同,突出显示了药物研究中生长阶段的重要性.
科学领域:
- 微生物学 微生物学
- 生物物理学的生物物理.
背景情况:
- 细菌表现出不同的生长阶段,影响细胞特性.
- 格拉姆阴性细菌具有复杂的双膜外,使药物透研究复杂化.
- 在非生长的细菌阶段,药物的有效性往往会下降,这可能导致多药性耐药性.
研究的目的:
- 为了研究不同生长阶段细菌外内的变化.
- 在生长过程中量化细菌膜和细菌区间的药物透和积累.
- 了解细菌生命周期对药物运输动力学的影响.
主要方法:
- 使用了非线性光学技术,第二波生成 (SHG) 谱学.
- 在大肠杆菌中探测了四级化合物 (QAC) 的运输动力学和积累,如马拉绿色.
- 采用光显微镜研究另一种QAC,化.
主要成果:
- 与缓慢或不生长的细胞相比,活跃生长的细胞表现出明显更快的药物运输和更高的细胞质积累.
- 鉴定出 *rpoS* 基因在和生长阶段对调节药物运输至关重要.
- 细菌膜的透性在随后的生长阶段开始之前呈现逐渐的变化.
结论:
- 细菌生长阶段是药物运输和积累的关键决定因素.
- 了解膜透性的生长阶段依赖性变化对于预测药物疗效至关重要.
- 报告细菌生长速度和阶段对于准确的药物疗效评估至关重要.
相关概念视频
Carrier-Mediated Transport
317
Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
317
Passive Diffusion: Overview and Kinetics
428
Passive diffusion is a critical process that allows small lipophilic drugs to cross the cell membrane along a concentration gradient. This mechanism's efficiency depends on four primary factors: the membrane's surface area, the drug's lipid-water partition coefficient, the concentration gradient, and the membrane's thickness.
When administered orally, drugs establish a substantial concentration gradient between the gastrointestinal (GI) lumen and the bloodstream, expediting...
When administered orally, drugs establish a substantial concentration gradient between the gastrointestinal (GI) lumen and the bloodstream, expediting...
428
Drug Absorption Mechanism: Passive Membrane Transport
3.7K
Passive transport is a method of drug absorption where small, lipid-soluble drugs can move across the cell membrane. This movement happens along the concentration gradient, which is a natural flow from higher to lower concentration areas. The speed at which the drug moves is directly related to its lipid–water partition coefficient. This means that the more a drug dissolves in lipids, the faster it diffuses or spreads throughout the body. It is important to note that most drugs are either...
3.7K
Cellular Membranes and Drug Transport
371
Drugs must traverse multiple biological barriers, such as multi-layered skin, single-layered intestinal epithelium, and the plasma membrane, to reach their target sites within the body. The plasma membrane, a highly structured composite of phospholipids, carbohydrates, and proteins, is the cell's protective boundary, facilitating selective substance exchange.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
Phospholipids arrange themselves into a bilayer, with hydrophilic heads oriented outward and hydrophobic tails facing inward.
371
Drug Elimination by Renal Route: Tubular Secretion
2.3K
Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
2.3K


