the role of coupled positive feedback in the expression of the spi1 type three secretion system in salmonella耦合的正反馈的作用在表达spi1三型分泌系统的沙门氏菌.pdfVIP

The Role of Coupled Positive Feedback in the Expression of the SPI1 Type Three Secretion System in Salmonella 1 2 2,3 1 Supreet Saini , Jeremy R. Ellermeier , James M. Slauch , Christopher V. Rao * 1 Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America, 2 Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America, 3 College of Medicine, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America Abstract Salmonella enterica serovar Typhimurium is a common food-borne pathogen that induces inflammatory diarrhea and invades intestinal epithelial cells using a type three secretion system (T3SS) encoded within Salmonella pathogenicity island 1 (SPI1). The genes encoding the SPI1 T3SS are tightly regulated by a network of interacting transcriptional regulators involving three coupled positive feedback loops. While the core architecture of the SPI1 gene circuit has been determined, the relative roles of these interacting regulators and associated feedback loops are still unknown. To determine the function of this circuit, we measured gene expression dynamics at both population and single-cell resolution in a number of SPI1 regulatory mutants. Using these data, we constructed a mathematical model of the SPI1 gene circuit. Analysis of the model predicted that the circuit serves two functions. The first is to place a threshold on SPI1 activation, ensuring that the genes encoding the T3SS are expressed only in response to the appropriate combination of environmental and cellular cues. The second is to amplify SPI1 gene expression. To expe