药物输送的动态决定了细菌对抗生素反应的演变过程
John C Crow1, Hao Geng1, Timothy J Sullivan2
1Department of Microbiology & Immunology, Dartmouth - Geisel School of Medicine, Hanover, NH 03755, USA.
bioRxiv : the preprint server for biology
|December 11, 2023
概括
微生物进化取决于环境变化动态. 逐渐的药物会增加微调耐药性,而突然的剂量会导致大肠杆菌的调节丧失.
科学领域:
- 微生物遗传学和进化研究
- 环境适应环境适应
- 药物耐药性机制 药物耐药性机制
背景情况:
- 微生物通过受调节的遗传机制适应环境变化.
- 环境变化动态在微生物进化中的作用尚未完全理解.
- 了解适应对于医学和生物技术等领域至关重要.
研究的目的:
- 研究环境变化速度如何影响微生物进化和适应.
- 确定不同药物管理动态对大肠杆菌耐药性的遗传机制的影响.
- 阐明在动态环境中导致耐药性的进化途径.
主要方法:
- 在不同的药物度动态下,对四环素耐药的大肠杆菌 (E. coli) 的实验演变.
- 连续培养实验与受控药物管理方案 (逐渐增加与周期性高剂量).
- 数学建模用于模拟和分析微生物对环境突发挑战的反应.
主要成果:
- 在逐渐增加药物的培养下,在替代性排泄中进化了微调突变.
- 在定期高剂量的药物下,培养物获得了转体子插入,导致了初级耐药机制调节的丧失.
- 数学模型证实,快速暴露于药物会压倒受调节的抵抗反应.
结论:
- 环境变化的动态在很大程度上影响了微生物的进化轨迹.
- 突然的环境变化可能导致对基本抵抗机制的监管控制丧失.
- 这些发现提供了关于临床耐药病原体中经常出现的调节损失的见解.
相关概念视频
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
208
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
208
Biopharmaceutics and Pharmacokinetics: Overview
2.0K
Understanding drugs, drug products, and their performance in pharmaceutical science is pivotal. Drugs, whether simple molecules or complex compounds, are designed to interact with the body's biological systems to diagnose, treat, or prevent diseases. Drug products include various delivery systems such as tablets, capsules, injections, and inhalers. The performance of these drug products is gauged by their ability to deliver the active ingredient to the desired site of action at the...
2.0K
Factors Influencing Drug Absorption: Drug Dissolution
520
The pharmacokinetic journey of drugs from solid oral dosage forms into systemic circulation is multifaceted. It begins with disintegration, a prerequisite ensuring a solid dosage form's subdivision into minute particles. Dissolution occurs next as these granulated entities solubilize in gastrointestinal fluids. This solubilization is crucial for the succeeding stage, permeation, which describes the traversal of the drug across the intestinal membrane and its subsequent entry into the blood...
520
Combined Effects of Drugs: Synergism
3.9K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
3.9K
Antibiotic Selection
54.1K
Overview
54.1K
Drug Delivery: Overview
296
The selection of a drug's delivery route depends upon its physicochemical properties, including lipid or water solubility and ionization, as well as the therapeutic requirement, such as immediate or sustained effect. These routes can be divided into three primary categories: enteral, parenteral, and topical.
Enteral delivery involves administering drugs directly through swallowing, sublingual placement, or buccal application. Orally administered drugs predominantly navigate the...
Enteral delivery involves administering drugs directly through swallowing, sublingual placement, or buccal application. Orally administered drugs predominantly navigate the...
296


