Martin Schuster
Bacterial communication, genomics, gene regulation, biofilms, pathogenesis, Pseudomonas aeruginosa.
Research Interests: Molecular microbiology: Bacterial communication
Office: 422 Nash Hall
Courses taught: MB 430/530 Bacterial Pathogenesis
Degrees: University of North Carolina, Chapel Hill
Research
Mechanistic and evolutionary aspects of quorum sensing in 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 two complete acyl-HSL signaling systems and one orphan receptor to control the expression of large, overlapping sets of target genes (Fig. 1). 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 laboratory 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 for group behavior. We are also interested in the evolution of cooperative traits and the ecological context of cell-cell signaling in bacteria. We have begun to explore this aspect by characterizing defectors that do not engage in social behavior. In P. aeruginosa, such cheaters emerge in the form of lasR mutants that cease production of extracellular quorum-controlled factors and take advantage of their production by the group.
For our studies, we employ a wide variety of classic and contemporary techniques, encompassing genomics, genetics, biochemistry, and physiology.
Selected Publications
Pub Med
Sandoz, K.M., Mitzimberg, S.M. and Schuster, M. (2007) Social cheating in Pseudomonas aeruginosa quorum sensing. Proc. Natl. Acad. Sci. USA 104: 15876-81
Schuster, M and Greenberg, E.P. (2007) Early activation of quorum sensing in Pseudomonas aeruginosa reveals the architecture of a complex regulon. BMC Genomics 8: 287
Schuster, M and Greenberg, E.P. (2006) A network of networks: Quorum sensing gene regulation in Pseudomonas aeruginosa. Int. J. Med. Microbiol. 296:73-81
Sonnleitner, E., Schuster, M., Sorger-Domenigg, T., Greenberg, E.P., Blasi, U. (2006) Hfq-dependent alterations of the transcriptome profile and effects on quorum sensing in Pseudomonas aeruginosa. Mol. Microbiol. 59: 1542-1558
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., Hetzer, M., Ciofu, O., Givskov, M., Greenberg, E.P., Holby, N. (2004) Pseudomonas aeruginosa biofilms exposed to imipenem exhibit changes in global gene expression and beta-lactamase and alginate production. Antimicrob. Agenst Chemother. 48:1175-1187
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