Genomics of Bacterium-Host Interactions: BIOMI/PLPA 6080

Lecture 9/20/10

Pathogenomics lessons from the Pseudomonadaceae

  1. Pseudomonas aeruginosa and P. syringae are members of a group of metabolically versatile, environmentally ubiquitous, fluorescent pseudomonads in the gamma-proteobacteria (Anzai et al. 2000).
  2. P. aeruginosa is the quintessential opportunistic pathogen and causes acute infections in burn victims, chronic infections in cystic fibrosis patients, and a variety of diseases in immunocompromised patients (Rahme et al. 2000).
  3. P. aeruginosa pathogenomics research initially was focused on two fully sequenced, reference strains: first PAO1 and later PA14 (Lee et al. 2006; Stover et al. 2000).
  4. P. aeruginosa PA14 is a multi-kingdom pathogen with disease models involving many eukaryotes, including Arabidopsis, lettuce and other plants, C. elegans, Galleria mellonella, and burned mice (Rahme et al. 2000).
  5. PA14 has two pathogenicity islands, PAP-1 and PAP-2, which harbor plant and animal virulence genes that are missing from PAO1 (He et al. 2004).
  6. Analysis of the virulence-related genomic islands of multiple P. aeruginosa strains reveals that virulence is combinatorial (Lee et al. 2006).
  7. P. aeruginosa adapts during years of chronic infection of the airways of cystic fibrosis patients through a variety of mutations that alter virulence(Smith et al. 2006).
  8. Hypermutation plays a major role in P. aeruginosa genome evolution during chronic respiratory infection (Mena et al. 2008).
  9. Ordered transposon libraries reveal a common set of essential genes in P. aeruginosa and provide an important genome-enabled resource (Jacobs et al. 2003; Liberati et al. 2006).
  10. A community database and comparative genome viewer provides several useful tools for thePseudomonas functional genomics community (Winsor et al. 2009).
  11. The potential for niche adaptation through the ability to gain and discard genomic segments is a major force driving the evolution of P. aeruginosa(Mathee et al. 2008).
  12. Comparison of multiple P. aeruginosa genomes in the context of multiple functional genomics studies highlights classes of genes encoding potentially useful targets for new antibioltics(Dotsch et al. 2010).
  13. The availability of an ordered transposon library enabled genomewide identification of genetic determinants of antimicrobial drug resistance in P. aeruginosa(Dotsch et al. 2009)
  14. CLINICAL APPLICATION BONUS TOPIC: Proteomics and next-generation sequencing of the emerging pathogen Parachlamydiaacanthamoebae were combined in a “dirty genome” approach for rapid identification of immunogenic proteins (Greub et al. 2009).

References

Anzai, Y., Kim, H., Park, J. Y., Wakabayashi, H., and Oyaizu, H. 2000. Phylogenetic affiliation of the pseudomonads based on 16S rRNA sequence. Int. J. Syst. Evol. Microbiol. 50:1563-1589.

Dotsch, A., Becker, T., Pommerenke, C., Magnowska, Z., Jansch, L., and Haussler, S. 2009. Genomewide identification of genetic determinants of antimicrobial drug resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother 53:2522-31.

Dotsch, A., Klawonn, F., Jarek, M., Scharfe, M., Blocker, H., and Haussler, S. 2010. Evolutionary conservation of essential and highly expressed genes in Pseudomonas aeruginosa. BMC Genomics 11:234.

Greub, G., Kebbi-Beghdadi, C., Bertelli, C., Collyn, F., Riederer, B. M., Yersin, C., Croxatto, A., and Raoult, D. 2009. High throughput sequencing and proteomics to identify immunogenic proteins of a new pathogen: the dirty genome approach. PLoS One 4:e8423.

He, J., Baldini, R. L., Deziel, E., Saucier, M., Zhang, Q., Liberati, N. T., Lee, D., Urbach, J., Goodman, H. M., and Rahme, L. G. 2004. The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes. Proc. Natl. Acad. Sci. USA 101:2530-2535.

Jacobs, M. A., Alwood, A., Thaipisuttikul, I., Spencer, D., Haugen, E., Ernst, S., Will, O., Kaul, R., Raymond, C., Levy, R., Chun-Rong, L., Guenthner, D., Bovee, D., Olson, M. V., and Manoil, C. 2003. Comprehensive transposon mutant library of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 100:14339-14344.

Lee, D. G., Urbach, J. M., Wu, G., Liberati, N. T., Feinbaum, R. L., Miyata, S., Diggins, L. T., He, J., Saucier, M., Deziel, E., Friedman, L., Li, L., Grills, G., Montgomery, K., Kucherlapati, R., Rahme, L. G., and Ausubel, F. M. 2006. Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial. Genome Biol. 7:R90.

Liberati, N. T., Urbach, J. M., Miyata, S., Lee, D. G., Drenkard, E., Wu, G., Villanueva, J., Wei, T., and Ausubel, F. M. 2006. An ordered, nonredundant library of Pseudomonas aeruginosa strain PA14 transposon insertion mutants. Proc Natl Acad Sci U S A 103:2833-8.

Mathee, K., Narasimhan, G., Valdes, C., Qiu, X., Matewish, J. M., Koehrsen, M., Rokas, A., Yandava, C. N., Engels, R., Zeng, E., Olavarietta, R., Doud, M., Smith, R. S., Montgomery, P., White, J. R., Godfrey, P. A., Kodira, C., Birren, B., Galagan, J. E., and Lory, S. 2008. Dynamics of Pseudomonas aeruginosa genome evolution. Proc Natl Acad Sci U S A 105:3100-5.

Mena, A., Smith, E. E., Burns, J. L., Speert, D. P., Moskowitz, S. M., Perez, J. L., and Oliver, A. 2008. Genetic adaptation of Pseudomonas aeruginosa to the airways of cystic fibrosis patients is catalyzed by hypermutation. J Bacteriol 190:7910-7.

Rahme, L. G., Ausubel, F. M., Cao, H., Drenkard, E., Goumnerov, B. C., Lau, G. W., Mahajan-Miklos, S., Plotnikova, J., Tan, M. W., Tsongalis, J., Walendziewicz, C. L., and Tompkins, R. G. 2000. Plants and animals share functionally common bacterial virulence factors. Proc. Natl. Acad. Sci. U S A 97:8815-8821.

Smith, E. E., Buckley, D. G., Wu, Z., Saenphimmachak, C., Hoffman, L. R., D'Argenio, D. A., Miller, S. I., Ramsey, B. W., Speert, D. P., Moskowitz, S. M., Burns, J. L., Kaul, R., and Olson, M. V. 2006. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc Natl Acad Sci U S A 103:8487-92.

Stover, C. K., Pham, X. Q., Erwin, A. L., Mizoguchi, S. D., Warrener, P., Hickey, M. J., Brinkman, F. S., Hufnagle, W. O., Kowalik, D. J., Lagrou, M., Garber, R. L., Goltry, L., Tolentino, E., Westbrock-Wadman, S., Yuan, Y., Brody, L. L., Coulter, S. N., Folger, K. R., Kas, A., Larbig, K., Lim, R., Smith, K., Spencer, D., Wong, G. K., Wu, Z., and Paulsen, I. T. 2000. Complete genome sequence of Pseudomonas aeruginosa PA01, an opportunistic pathogen. Nature 406:959-964.

Winsor, G. L., Van Rossum, T., Lo, R., Khaira, B., Whiteside, M. D., Hancock, R. E., and Brinkman, F. S. 2009. Pseudomonas Genome Database: facilitating user-friendly, comprehensive comparisons of microbial genomes. Nucleic Acids Res 37:D483-8.