Kinetics of Bacterial Adaptation, Growth, and Death at Didecyldimethylammonium Chloride sub-MIC Concentrations

Abstract

Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) are standard indexes for determining disinfection effectiveness. Nevertheless, they are static values disregarding the kinetics at sub-MIC concentrations where adaptation, growth, stationary, and death phases can be observed. The understanding of these dynamic mechanisms is crucial to designing effective disinfection strategies. In this study, we studied the 48 h kinetics of Bacillus cereus and Escherichia coli cells exposed to sub-MIC concentrations of didecyldimethylammonium chloride (DDAC). Two mathematical models were employed to reproduce the experiments: the only-growth classical logistic model and a mechanistic model including growth and death dynamics. Although both models reproduce the lag, exponential and stationary phases, only the mechanistic model is able to reproduce the death phase and reveals the concentration dependence of the bactericidal/bacteriostatic activity of DDAC. This model could potentially be extended to study other antimicrobials and reproduce changes in optical density (OD) and colony-forming units (CFUs) with the same parameters and mechanisms of action.

Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications

“…Pedreira et al. studied the sterilization kinetics of DDAC under sub-MIC, thereby deriving a completely new mathematical model capable of reproducing net growth and death kinetics, which revealed concentration depends on the bactericidal or bacteriostatic activity of DDAC . Another example is a survey of hospital intensive care unit patients.…”

Mechanisms ofListeria monocytogenesdisinfection with Benzalkonium chloride: from molecular dynamics to kinetics of time-kill curves

“…The main assumption is that cells die when a sufficient concentration of BAC is integrated into the membrane using the rational model, common in chemical disinfection (16): where N is the bacterial concentration at anytime, k d is the constant of the inactivation rate, n the concentration of dilution and x the constant describing the behavior of shoulders ( x < 1) or tailing ( x > 1) behavior. However, instead of directly using the disinfectant dose, we make the kill curve dependent on the disinfectant concentration on the membrane C m following a Hill function, a common model in pharmacokinetic and pharmacodynamic (17) and previously used to describe other QAC disinfection dynamics (18). Therefore, the model reads: where k m is the half maximal effective concentration (disinfectant concentrations at which 50% of the maximum effect is obtained) and n is the Hill coefficient shaping the effect of the disinfectant (higher values model sharp functions, similar to step functions with only two possible values, and low values simulates a sigmoid curve).…”

“…We modified the rational model to make the time-kill curves dependent on the disinfectant concentration on the membrane C m following a Hill function. Note that this approach is widely used in pharmacokinetics and pharmacodynamics (Mouton and Vinks, 2005) and has been applied to describe other QAC disinfection dynamics (Pedreira et al, 2022). As a result, the model reads: where k m is the half-maximal effective concentration (disinfectant concentrations at which 50% of the maximum effect is obtained) and n is the Hill coefficient that shapes the effect of the disinfectant (higher values model sharp functions, similar to step functions with only two possible values, and low values simulate a sigmoid curve).…”

“…where N is the bacterial concentration at any time, k d is the constant of the inactivation rate, n the concentration of dilution and x the constant describing the behavior of shoulders (x < 1) or tailing (x > 1) behavior. However, instead of directly using the disinfectant dose, we make the kill curve dependent on the disinfectant concentration on the membrane C m following a Hill function, a common model in pharmacokinetic and pharmacodynamic (17) and previously used to describe other QAC disinfection dynamics (18). Therefore, the model reads:…”

Control predictivo basado en modelo como alternativa al modo de operación estándar en morbidostato

“…Mientras la EAL ha resultado fundamental para entender las adaptaciones inducidas por variables abióticas, como la temperatura, en los últimos tiempos el rápido aumento en el número de bacterias resistentes a los antimicrobianos está siendo el centro de un sinfín de estudios. Cuando se analizan los efectos de las sustancias antimicrobianas sobre las bacterias, éstas pueden ser capaces de eliminar (bactericidas) o de inhibir el crecimiento (bacteriostáticas) de la población empleando unas dinámicas de modelado muy características, que todavía generan controversia [2,18]. Los compuestos que actualmente inducen resistencia en las bacterias no abarcan únicamente los antibióticos, sino muchas otras substancias tales como los desinfectantes, debido al aumento de su uso (o a su uso inadecuado) durante la pandemia [17,14,16].…”