Phenotypic memory in quorum sensing

Abstract

Quorum sensing (QS) is a regulatory mechanism used by bacteria to coordinate group behavior in response to high cell densities. During QS, cells monitor the concentration of external signals, known as autoinducers, as a proxy for cell density. QS often involves positive feedback loops, leading to the upregulation of genes associated with QS signal production and detection. This results in distinct steady-state concentrations of QS-related molecules in QS-ON and QS-OFF states. Due to the slow decay rates of biomolecules such as proteins, even after removal of the initial stimuli, cells can retain elevated levels of QS-associated biomolecules for extended periods of time. This persistence of biomolecules after the removal of initial stimuli has the potential to impact the response to future stimuli, denoting a memory of past exposure. This phenomenon, which is a consequence of the carry-over of biomolecules rather than genetic inheritance, is known as "phenotypic" memory. This theoretical study aims to investigate the presence of phenotypic memory in QS and the conditions that influence this memory. Numerical simulations based on ordinary differential equations and analytical modeling were used to study gene expression in response to sudden changes in cell density and extracellular signal concentrations. The model examined the effect of various cellular parameters on the strength of QS memory and the impact on gene regulatory dynamics. The findings revealed that QS memory has a transient effect on the expression of QS-responsive genes. These consequences of QS memory depend strongly on how cell density was perturbed, as well as various cellular parameters, including the Fold Change in the expression of QS-regulated genes, the autoinducer synthesis rate, the autoinducer threshold required for activation, and the cell growth rate. Author summaryBacteria use a mechanism known as quorum sensing (QS) to collaborate when their numbers are high. Cells produce and detect signals that trigger the production of certain proteins and changes in cell behavior. Interestingly, the molecules produced during this process can linger even after the initial signal is gone. The persistence of these molecules is a form of "memory", as cells are temporarily changed by events in the recent past. Our theoretical study focuses on exploring this memory and the factors that influence it. To do this, we used simulations and models to examine how history of exposure to signals can affect the future response of cells. We found that the prior exposure to signals can influence how bacteria respond in the future, but this memory only has consequences under specific conditions. This research contributes to our understanding of quorum sensing and how bacteria adapt to environmental changes.