Our research program seeks answers to a fundamental biological question:
How does an organism know when, where and for long to turn a gene on or off?
We address this question by investigating bacterial species
that establish intimate interactions with animal hosts.
Visit our Research page for more information.
Schematic depicting the regulatory circuit engineered to promote cellulose biosynthesis in response to the signals activating the phoP promoter.
Salmonella promotes virulence by repressing cellulose production.
(S5B) Schematic depicting the regulatory circuit engineered to promote cellulose biosynthesis in response to the signals activating the phoP promoter.
The PhoP/PhoQ system promotes surface motility on low Mg2+ agarose media.
B. thetaiotaomicron dynamically adjusts transcription of CS PUL genes to the CS catabolic rate.
Species-specific dynamic responses of gut bacteria to a mammalian glycan.
B. thetaiotaomicron dynamically adjusts transcription of CS PUL genes to the CS catabolic rate. (Top) The porin BT3332 and its partner, BT3331, transport CS across the outer membrane and into the periplasmic space, where it is converted into unsaturated chondroitin disaccharides by the action of three distinct CS lyases (BT3324, BT3350, and BT4410). Unsaturated disaccharides are broken down by the glucuronyl hydrolase BT3348 into the monosaccharides N-acetylgalactosamine (GalNAc) and 5-keto-4-deoxyuronate (kdu). Particular unsaturated disaccharides that are substrates for the glucuronyl hydrolase serve as activating ligands that bind to the periplasmic domain of the hybrid two-component system regulator BT3334, which governs the transcription of CS utilization genes. (Middle) A cluster of BT3334-regulated genes from the CS PUL is also depicted (the schematic is not drawn to scale). (Bottom) Expression of BT3334-regulated genes, represented by the sulfatase 1 (BT3333) mRNA, initially increases when unsaturated disaccharides are produced and then falls when the levels and activity of the rate-limiting glucuronyl hydrolase rise. The mRNA levels depicted are normalized to a 1,000-fold dilution of 16S rRNA, and the indicated fold change (i.e., 30×) denotes the ratio of mRNA levels at 120 min postinduction to the levels before induction (16).
Regulation of the mgtCBR virulence operon by ATP and proline tRNAPro.
Control of a Salmonella virulence operon by proline-charged tRNA(Pro).
Regulation of the mgtCBR virulence operon by ATP and proline tRNAPro. The phosphorylated PhoP protein binds to the promoter of the mgtCBR operon and stimulates transcription initiation. The 296-long mgtCBRleader mRNA harboring two short ORFs (termed mgtM and mgtP) controls transcription elongation into the coding region in response to ATP and proline tRNAPro levels. Proline tRNAPro levels determine the coupling/uncoupling between transcription of the mgtCBR leader and translation of mgtP, allowing formation of one of two alternative stem-loop structures (stem loop D versus E), hence controlling transcription elongation into the mgtCBR coding region. The sequences of mgtP variants used in this work are indicated above the Pro codons.
Model for the mechanism of prolonged, Mg2+-sensitive pausing in the mgtA leader.
Model of regulation of the PhoP/PhoQ system by different signals.
When Too Much ATP Is Bad for Protein Synthesis.
Reciprocal Control between a Bacterium's Regulatory System and the Modification Status of Its Lipopolysaccharide.
The PmrA/PmrB regulatory system promotes modification of the bacterial cell surface.
Some of these modifications limit access of an inducing signal for the sensor PmrB.
A decrease in active regulator PmrA lowers expression of modifying determinants.
The activity of a regulatory system can change dynamically under inducing conditions.
The bacterial transcription termination factor Rho coordinates Mg2 + homeostasis with translational signals.
The unusually long and highly conserved corA leader mRNA can adopt two mutually exclusive conformations that determine whether or not Rho interacts with a Rho utilization (rut) site on the nascent RNA and thereby prevents transcription of the corA coding region. The RNA conformation that promotes Rho-dependent termination is favored by efficient translation of corL, a short open reading frame located within the corA leader. Thus, corA transcription is inversely coupled to corL translation. This mechanism resembles those governing expression of Salmonella's other two Mg2+ transport genes, suggesting that Rho links Mg2+ uptake to translational signals.
An RNA motif advances transcription by preventing Rho-dependent termination.
Fig. 5. Model of transcription termination control by the mgtCBR leader. (A) Schematic of the DNA region corresponding to the mgtCBR leader. Small ORFs are indicated by pink and white arrows; the position of RARE and rut are indicated by rectangles, and transcription pause sites (Fig. 2C) by open boxes. The leader RNA emerges from the transcribing RNAP and folds into stem-loop A. (B) When translation is efficient, the ribosome translating mgtM unwinds stem-loop A, allowing folding of stem-loop B, which sequesters RARE. Rho loads onto the RNA and translocates toward a paused RNAP. Rho triggers transcription termination, thereby turning mgtCBR expression OFF. (C) When translation is inefficient, single-stranded RARE traps Rho in an inactive state. Transcription continues, turning mgtCBR expression ON.