Ph.D. 2000, University of North Carolina, Chapel HIll
KEYWORDS: Bacterial Communication; Genomics; Signal Transduction; Gene Regulation; Biofilms; Pathogenesis; Pseudomonas aeruginosa
Bacterial cell-to-cell signaling, termed quorum sensing, has emerged as a new field in microbiology. Individual bacteria use chemical signals to communicate with each other and coordinate group activities. The best understood signaling system employs diffusable acyl-homoserine lactone (acyl-HSL) molecules that are made by an acyl-HSL synthase and are bound by a cognate receptor that acts as a transcriptional activator. There are now over 70 known examples of such components in bacterial species. The opportunistic human pathogen Pseudomonas aeruginosa serves as a model system to study quorum sensing gene regulation. It employs at least two acyl-HSL signaling systems to control the expression of two large, overlapping sets of target genes. In addition to its function as a global regulator of gene expression, quorum sensing in P. aeruginosa is also important for virulence and the formation of biofilms, surface-associated bacterial communities, which have been implicated in chronic persistent infection. As such, quorum sensing has become an important target for antimicrobial and antibiofilm strategies.
Our group investigates the molecular mechanisms of quorum sensing gene regulation in Pseudomonas aeruginosa, including the identity of target genes, promoter specificity, quorum signal binding, integration of quorum sensing into cellular physiology, and the role of the two quorum sensing systems during biofilm formation. We employ a wide variety of classic and contemporary techniques, encompassing genomics, genetics, biochemistry, and physiology.
Schuster, M., Urbanowski, M.L., and Greenberg, E.P. (2004) Promoter specificity in Pseudomonas aeruginosa quorum sensing revealed by DNA binding of purified LasR. Proc. Natl. Acad. Sci. USA 101: 15833-15877
Bagge, N., Schuster, M., Hentzer, M., Ciofu, O., Givskov, M., Greenberg, E.P., Hoiby, N. (2004) Pseudomonas aeruginosa biofilms exposed to imipenem exhibit changes in global gene expression and beta-lactamase and alginate production. Antimicrob. Agents Chemother. 48: 1175-1187
Schuster, M., Hawkins, A.C., Harwood, C.S., and Greenberg, E.P. (2004) The Pseudomonas aeruginosa RpoS regulon and its relationship to quorum sensing. Mol. Microbiol. 51: 973-985
Schuster, M., Lostroh, C.P., Ogi, T., and Greenberg, E.P. (2003) Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J. Bacteriol. 185: 2066-2079
Schuster, M., Silversmith, R.E., and Bourret, R.B. (2001) Conformational coupling in the chemotaxis response regulator CheY. Proc. Natl. Acad. Sci. USA 98: 6003-6008
Schuster, M., Zhao, R., Bourret, R.B., and Collins, E.J. (2000) Correlated switch binding and signaling in bacterial chemotaxis. J. Biol. Chem. 275: 19752-19758
Abouhamad, W.N., Bray, D., Schuster, M., Boesch, K.C., Silversmith, R.E., and Bourret, R.B. (1998) Computer aided resolution of an experimental paradox in bacterial chemotaxis. J. Bacteriol. 180: 3757-3764
Ramakrishnan, R., Schuster, M., and Bourret, R.B. (1998) Acetylation at Lys92 enhances signaling by the chemotaxis response regulator CheY. Proc. Natl. Acad. Sci. USA 95: 4918-4923
Schuster, M., Abouhamad, W.N., Silversmith, R.E., and Bourret, R.B. (1998) Chemotactic response regulator mutant CheY95IV exhibits enhanced binding to the flagellar switch and phosphorylation dependent constitutive signalling. Mol. Microbiol. 27: 1065-1077.