Pseudomonas aeruginosa Genomics and Systems Biology

In the past 16 years we made significant contributions to Pseudomonas functional genomics. We co-authored the first (and fourth) genome sequence paper, co-run the Pseudomonas genome web page with Fiona Brinkman, Simon Fraser University, and provide lux mutants from our library to the community. Using these resources we have made many new contributions to understanding the surfaces, antibiotic susceptibility and resistance (particularly adaptive resistance), and environmental/pathogenesis adaptations of this organism.

In particular we have been recently trying to understand adaptive lifestyles. Pseudomonas aeruginosa has evolved complex interwoven regulatory mechanisms that permit adaptation to a wide variety of circumstances and environments (including antibiotic, nutritional and other environmental stresses, and particular growth states such as swarming and surfing motility and biofilm formation that are thought to represent distinct lifestyles in the body). We have addressed these issues using the 3 comprehensive arrayed mutant libraries available to us, as well as global transcriptional profiling (RNA-Seq). Generally speaking this reveals massive complexity. For example, swarming motility is a complex form of surface motility triggered by semi-viscous medium and a weak nitrogen source (such as amino acids). In swarming motility we identified more than 1600 genes (85 regulators) that were dysregulated under swarming conditions including upregulation of most virulence factors, alterations in metabolism and changes in antibiotic resistance genes; mutant library screens identified 233 genes essential to this process (mutants largely prevented swarming), including 35 regulators. We have characterized some of the regulators in great detail, such as CbrAB/CrcZ/Crc and MetR, including a detailed characterization of their roles in motility, biofilm formation, production of various virulence factors, growth in vivo and antibiotic resistance. Similar detailed studies are underway for other complex adaptations and we are particularly interested deciphering the multidrug adaptive resistance that accompanies these growth states.

References

Complete genome sequence of Pseudomonas aeruginosa: an opportunistic pathogen

Stover, K.C., X.Q. Pham, A.L. Erwin, S.D. Mizoguchi, P. Warrener, M.J. Hickey, F.S.L. Brinkman, W. O. Hufnagle, D.J. Kowalik, M. Lagrou, R.L. Garber, L. Goltry, E. Tolentino, S. Westbrock-Wadman, Y. Yuan, L.L. Brody, S.N. Coulter, K.R. Folger, A. Kas, R. Lim, K. Smith, D. Spencer, G.K.-S. Wong, Z. Wu, I. Paulsen, J. Reizer, M.H. Saier, R.E.W. Hancock, S. Lory, and M.V. Olson. (2000) Nature 406: 959-964 PDF