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前动力学与前反应动力学:抗生素抗性生物分子的动力学与反应动力学

Antechodynamics and Antechokinetics: Dynamics and Kinetics of Antibiotic Resistance Biomolecules.

作者信息

Baquero F, Cantón R, Pérez-Cobas A E, Coque T M, Levin B, Rodríguez-Beltrán J

机构信息

Department of Microbiology, Ramón y Cajal University Hospital, Ramón y Cajal Institute for Health Research (IRYCIS), 28034 Madrid, Spain.

Network Center for Research in Epidemiology and Public Health (CIBERESP), 28034 Madrid, Spain.

出版信息

Biomolecules. 2025 Jun 5;15(6):823. doi: 10.3390/biom15060823.

Abstract

The pharmacology of antimicrobial agents comprises pharmacodynamics and pharmacokinetics. Pharmacodynamics refers to studying drugs' mode of action on their molecular targets at various concentrations and the resulting effect(s). Pharmacokinetics refers to studying the way(s) in which drugs enter the body and are distributed to their targets in various compartments (such as tissues) and how local drug concentrations are modified in time, such as by metabolism or excretion. Pharmacodynamics and pharmacokinetics constitute pivotal knowledge for establishing the breakpoints used to identify the appropriate antimicrobial agents for infection therapy. Antibiotic resistance is the biological force opposing antimicrobials' pharmacological effects. However, we do not have a term similar to pharmacology for microbial antibiotic resistance reactions. Here, we propose the new scientific field of antechology (from the classic Greek , resistance), studying the dynamics and kinetics of antibiotic resistance molecules which oppose the effect of antimicrobial drugs. Antechodynamics refers to the study of the molecular mechanisms through which antibiotic molecules are chemically modified or degraded by particular bacterial resistance enzymes (primary effectors) or drive the modification of an antibiotic's target inhibition sites through molecules released by antibiotic action on the microorganism (secondary effectors). Antechokinetics refers to the study of the processes leading to bacterial spatial cellular (subcellular, pericellular, extracellular) localizations of the molecules involved in antibiotic detoxifying mechanisms. Molecules' local concentrations change over time due to their production, their degradation, and ultimately their excretion rates. We will examine the antechodynamics and antechokinetics for various antimicrobial classes and the relation between pharmacodynamics/pharmacokinetics and antechodynamics/antechokinetics.

摘要

抗菌药物的药理学包括药效学和药代动力学。药效学是指研究药物在不同浓度下对其分子靶点的作用方式以及产生的效果。药代动力学是指研究药物进入体内并分布到各个隔室(如组织)中的靶点的方式,以及局部药物浓度如何随时间变化,例如通过代谢或排泄。药效学和药代动力学是确定用于识别感染治疗合适抗菌药物的断点的关键知识。抗生素耐药性是对抗抗菌药物药理作用的生物学力量。然而,对于微生物抗生素耐药反应,我们没有一个类似于药理学的术语。在此,我们提出了新的科学领域——抗技术学(源自经典希腊语,意为“抗性”),研究对抗抗菌药物作用的抗生素耐药分子的动力学和动力学过程。抗药效学是指研究抗生素分子被特定细菌耐药酶(主要效应物)化学修饰或降解,或通过抗生素对微生物作用释放的分子驱动抗生素靶点抑制位点修饰的分子机制。抗药代动力学是指研究导致参与抗生素解毒机制的分子在细菌空间细胞(亚细胞、细胞周围、细胞外)定位的过程。由于分子的产生、降解以及最终的排泄速率,分子的局部浓度会随时间变化。我们将研究各类抗菌药物的抗药效学和抗药代动力学,以及药效学/药代动力学与抗药效学/抗药代动力学之间的关系。

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