High stimulus unmasks positive feedback in an autoregulated bacterial signaling circuit

Tim Miyashiro, Mark Goulian

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


We examined the effect of positive autoregulation on the steadystate behavior of the PhoQ/PhoP two-component signaling system in Escherichia coli. We found that autoregulation has no effect on the steady-state output for a large range of input stimulus, which was modulated by varying the concentration of magnesium in the growth medium. We provide an explanation for this finding with a simple model of the PhoQ/PhoP circuit. The model predicts that even when autoregulation is manifest across a range of stimulus levels, the effects of positive feedback on the steady-state output emerge only in the limit that the system is strongly stimulated. Consistent with this prediction, amplification associated with autoregulation was observed in growth-limiting levels of magnesium, a condition that strongly activates PhoQ/PhoP. In a further test of the model, we found that strains harboring a phosphatase-defective PhoQ showed strong positive feedback and considerable cell-to-cell variability under growth conditions where the wild-type circuit did not show this behavior. Our results demonstrate a simple and general mechanism for regulating the positive feedback associated with autoregulation within a bacterial signaling circuit to boost response range and maintain a relatively uniform and graded output.

Original languageEnglish (US)
Pages (from-to)17457-17462
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number45
StatePublished - Nov 11 2008

All Science Journal Classification (ASJC) codes

  • General


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