Noise and Stochasticity in Gene Expression:A Pathogenic Fate Determinant

Not all cells in a bacterial population exhibit exactly the same phenotype, even though they grow in the same environment and are genetically identical. This phenomenon is known as phenotypic variation. The major source of phenotypic variation is noise or stochasticity in gene expression networks, which can directly promote the formation of population heterogeneity. Bistability, or the existence of two stable subpopulations, is a direct outcome of gene expression noise. In this chapter, we will discuss the origin of noise in gene expression and how researchers measure, quantify and engineer noise in gene circuits. Furthermore, we will describe how pathogenic organisms utilize noisy gene circuits for bistable gene expression of virulence factors. This serves to highlight the importance of noise in molecular decision making. We discuss how two pathogenic bacteria employ heterogeneous gene expression when invading a host: firstly, the heterogeneously expression of pilus formation, which are thought to aid the colonization the Gram-positive bacterium Streptococcus pneumoniae by facilitating attachment to host epithelium, and, secondly, the complex gene circuit with positive and double-negative feedback loops characteristic for noise-driven expression, used by the Gram-negative bacterium Salmonella enterica serovar Typhimurium to regulate flagella formation and the expression of its type 3 secretion system