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Half a century has passed since the discovery of operons (groups of genes that are transcribed together as a single mRNA). Despite the importance of operons in bacterial gene networks, the relationship between their organization and gene expression remains poorly understood. Here we show using synthetic operons in Escherichia coli that the expression of a given gene increases with the length of the operon and as its position moves farther from the end of the operon. These findings can be explained by a common mechanism; increasing the distance from the start of a gene to the end of the operon (termed the "transcription distance") provides more time for translation to occur during transcription, resulting in increased expression. We confirmed experimentally that the increased expression is indeed due to increased translation. Furthermore our analysis indicates the translation initiation rate for an mRNA is sixfold greater during transcription than after its release, which amplifies the impact of the transcription distance on gene expression. As a result of these mechanisms, gene expression increases by ∼40% for each 1,000 nucleotides of transcription distance. In summary, we demonstrate that a fundamental relationship exists between gene expression and the number, length, and order of the genes in an operon. This relationship has important implications for understanding the functional basis of genome organization and practical applications for synthetic biology. Each operon consists of a group of adjacent genes that are cotranscribed as a single mRNA. It is estimated that 50% of the genes in Escherichia coli are transcribed at least some of the time as part of an operon (2). The organization of genes in operons can alter gene expression when specific regulatory mechanisms are present such as translational coupling (3), polarity (4), and/or feedback (5, 6). However, it is unclear whether operon organization has any impact on gene expression in the absence of these specific mechanisms.In this study we used synthetic operons to systematically examine whether the number, length, or order of the genes in an operon modulates gene expression. These synthetic operons lack the mRNA-specific, regulatory mechanisms commonly found in native operons. We found that gene expression increases with the distance between the start of a gene and the end of the operon ("transcription distance") due to increased translation. These findings reveal that operon organization can modulate levels and patterns of gene expression via a general mechanism. ResultsGene Expression Increases with Operon Length. The relationship between gene expression and operon length was examined in four sets of operons constructed with the genes encoding the cyan (cfp), yellow (yfp), and/or mCherry (rfp) fluorescent proteins ( Fig. 1 A-D and Fig. S1). The operons were constitutively transcribed from the pLlacO-1 promoter in the absence of the Lac repressor. The translation of the first gene in each operon was controlled by the highly efficient T710RBS7 ribosom...

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.

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