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

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 antechó, 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.