Phenotypic variation in bacteria: the role of feedback regulation

Key Points Even under laboratory conditions, bacteria often show a high degree of phenotypic variability — cells within an isogenic population displaying variable expression patterns. Positive feedback within a regulatory network has the potential to generate multistationarity — the possibility of a cell to switch between states. Bistability or multistability is the occurrence of two or more distinguishable phenotypes within the isogenic population. The ratio of cells within a specific cell state depends on the intrinsic properties of the switch and is often influenced and modulated by environmental signals. It was found that the molecular mechanism underlying phenotypic variation in a number of adaptive bacterial responses, such as competence and sporulation in Bacillus subtilis , is based on positive feedback. Many of the observed — but still unexplained — variable phenotypes reported within bacterial research are likely to originate from the feedback structure within the regulatory pathway. Phenotypic variability is a way to increase the fitness of the population, especially under fluctuating environmental conditions. This article focuses on phenotypic variation based on the feedback architecture of genetic networks, a type of variability that is epigenetic in nature, relies on direct or indirect autostimulation of pivotal transcription factors, and is observed in various bacterial systems. To survive in rapidly changing environmental conditions, bacteria have evolved a diverse set of regulatory pathways that govern various adaptive responses. Recent research has reinforced the notion that bacteria use feedback-based circuitry to generate population heterogeneity in natural situations. Using artificial gene networks, it has been shown that a relatively simple 'wiring' of a bacterial genetic system can generate two or more stable subpopulations within an overall genetically homogeneous population. This review discusses the ubiquity of these processes throughout nature, as well as the presumed molecular mechanisms responsible for the heterogeneity observed in a selection of bacterial species.