Induction and Relaxation Dynamics of the Regulatory Network Controlling the Type III Secretion System Encoded within Salmonella Pathogenicity Island 1

摘要: Abstract Bacterial pathogenesis requires the precise spatial and temporal control of gene expression, dynamics which are controlled by regulatory networks. A network encoded within Salmonella Pathogenicity Island 1 controls expression a type III protein secretion system involved in invasion host cells. The this measured single cells using promoter-green fluorescent (gfp) reporters flow cytometry. During induction, there is order with transcriptional inputs turning on first, followed structural effector genes. promoters show varying stochastic properties, where graded converted into all-or-none hybrid responses. relaxation shifting from inducing to noninducing conditions measuring fluorescence decay. gfp expressed controlling ( hilC hilD ) genes prgH decay exponentially, characteristic time 50–55 min. In contrast, promoter effectors sicA persists for 110 ± 9 min. This genetic circuit, formed transcription factor (InvF), chaperone (SicA), secreted (SipC), that regulates response capacity cell. mathematical model circuit demonstrates delay due split positive feedback loop. tested Δ knockout strain, complemented without eliminated when loop deleted. Furthermore, robustness analysis predicts can be tuned changing affinity SicA:InvF multimers an operator promoter. prediction used construct targeted library, contains mutants both longer shorter delays. combination theory experiments provides platform predicting how perturbations lead changes global network.