Research Departments & Organizations
Yale Microbial Sciences Institute
Molecular Mechanisms of Bacterial Signal Transduction
Summary: Eduardo Groisman is interested in understanding how pathogenic and symbiotic bacteria modulate their gene expression patterns in response to signals detected in host and in abiotic environments, as well as in how bacterial regulatory circuits evolve. Our laboratory investigates the mechanisms by which pathogenic and commensal bacteria modify their gene expression patterns so they can survive and proliferate within host tissues and in abiotic environments. We have focused on the mechanisms utilized by the gastroenteritis- and typhoid fever–causing Salmonella enterica, the bubonic plague agent Yersinia pestis, and the human gut commensal Escherichia coli. Our research program can be divided into three general areas: (1) the signal transduction pathways by which bacteria detect and integrate multiple signals into a cellular response, (2) the molecular mechanisms by which a regulatory protein or signal elicits distinct responses from coregulated targets, and (3) the genetic basis for the phenotypic differences that distinguish closely related bacterial species.
Specialized Terms: Bacterial genetics; Signal transduction; Infectious diseases; Gene regulation; Bacteria-host interactions; Gut commensal bacteria; Microbiome
Extensive Research Description
Our research 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.
All organisms respond to a change in their environment by modifying their behavior. We are interested in identifying the specific signals that denote a given environment, the nature of the sensors that detect such signals, and how the sensors transmit this information to the regulators implementing a response that enables the organism to survive and prosper in the new condition.
We investigate the gastroenteritis- and typhoid fever-causing Salmonella entericaand the gut symbiotic bacteria Escherichia coli and Bacteroides thetaiotaomicron.
We have been examining protein sensors that detect extracellular signals and RNA sensors that monitor cellular metabolites and ions. These investigations led both to the discovery of the first signal transduction systems that sense extracytoplasmic magnesium and ferric iron and to the first mRNAs that respond to cytoplasmic magnesium and ATP.
Our research focuses on understanding:
- how bacteria integrate multiple signals into a cellular response,
- the mechanisms by which a given signal elicits distinct responses from co-regulated targets,
- how bacteria from the gut microbiome compete for resources,
- the genetic basis for phenotypic differences that distinguish closely related bacterial species, such as a pathogen and a symbiont,
- the biochemical function of novel proteins and
- the genetic control of virulence factors.
A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium's own F1Fo ATP synthase.
Lee EJ, Pontes MH, Groisman EA. A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium's own F1Fo ATP synthase. Cell 2013, 154:146-56. 2013
The lipopolysaccharide modification regulator PmrA limits Salmonella virulence by repressing the type three-secretion system Spi/Ssa.
Choi J, Groisman EA. The lipopolysaccharide modification regulator PmrA limits Salmonella virulence by repressing the type three-secretion system Spi/Ssa. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110:9499-504. 2013
Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems.
Townsend GE, Raghavan V, Zwir I, Groisman EA. Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110:E161-9. 2013
Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA.
Lee EJ, Groisman EA. Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA. Nature 2012, 486:271-5. 2012