The Regulatory Network of Pseudomonas aeruginosa

Springer Science and Business Media LLC - Tập 1 - Trang 1-11 - 2011
Edgardo Galán-Vásquez1, Beatriz Luna1, Agustino Martínez-Antonio1
1Departamento de Ingeniería Genética, Cinvestav, Irapuato Gto, México

Tóm tắt

Pseudomonas aeruginosa is an important bacterial model due to its metabolic and pathogenic abilities, which allow it to interact and colonize a wide range of hosts, including plants and animals. In this work we compile and analyze the structure and organization of an experimentally supported regulatory network in this bacterium. The regulatory network consists of 690 genes and 1020 regulatory interactions between their products (12% of total genes: 54% sigma and 16% of transcription factors). This complex interplay makes the third largest regulatory network of those reported in bacteria. The entire network is enriched for activating interactions and, peculiarly, self-activation seems to occur more prominent for transcription factors (TFs), which contrasts with other biological networks where self-repression is dominant. The network contains a giant component of 650 genes organized into 11 hierarchies, encompassing important biological processes, such as, biofilms formation, production of exopolysaccharide alginate and several virulence factors, and of the so-called quorum sensing regulons. The study of gene regulation in P. aeruginosa is biased towards pathogenesis and virulence processes, all of which are interconnected. The network shows power-law distribution -input degree -, and we identified the top ten global regulators, six two-element cycles, the longest paths have ten steps, six biological modules and the main motifs containing three and four elements. We think this work can provide insights for the design of further studies to cover the many gaps in knowledge of this important bacterial model, and for the design of systems strategies to combat this bacterium.

Tài liệu tham khảo

Stover CK, Pham XQ, Erwin AL, Mizoguchi SD, Warrener P, Hickey MJ, Brinkman FS, Hufnagle WO, Kowalik DJ, Lagrou M, Garber RL, Goltry L, Tolentino E, Westbrock-Wadman S, Yuan Y, Brody LL, Coulter SN, Folger KR, Kas A, Larbig K, Lim R, Smith K, Spencer D, Wong GK, Wu Z, Paulsen IT, Reizer J, Saier MH, Hancock RE, Lory S, Olson MV: Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen. Nature. 2000, 406: 959-964. 10.1038/35023079. Klein J, Leupold S, Münch R, Pommerenke C, Johl T, Kärst U, Jänsch L, Jahn D, Retter I: ProdoNet: identification and visualization of prokaryotic gene regulatory and metabolic networks. Nucleic Acids Res. 2008, 36: W460-W464. 10.1093/nar/gkn217. Choi C, Münch R, Leupold S, Klein J, Siegel I, Thielen B, Benkert B, Kucklick M, Schobert M, Barthelmes J, Ebeling C, Haddad I, Scheer M, Grote A, Hiller K, Bunk B, Schreiber K, Retter I, Schomburg D, Jahn D: SYSTOMONAS- an integrated database for systems biology analysis of Pseudomonas. Nucleic Acids Res. 2007, 35: D533-D537. 10.1093/nar/gkl823. Winsor G, Van T, Lo R, Bhavjinder K, Whiteside M, Hancock R, Brinkman S: Pseudomonas Genome Database: facilitating user-friendly, comprehensive comparisons of microbial genomes. Nucleic Acids Res. 2009, 37: D483-D488. 10.1093/nar/gkn861. Perez-Rueda E, Janga SC, Martinez-Antonio A: Scaling relationship on the gene content of transcriptional machinery in bacteria. Mol. BioSyst. 2009, 12: 494-501. Réka A: Scale-free networks in cell biology. J. Cell Sci. 2005, 118: 4947-4957. 10.1242/jcs.02714. Watts J: The "new" science of networks. Annu. Rev. Sociol. 2004, 30: 243-270. 10.1146/annurev.soc.30.020404.104342. Erdõs P, Renyi A: On random graphs I. Publ. Math. 1959, 6: 290-297. Barabási A, Oltvai Z: Networks biology: understanding the cell's functional organization. Nat. Rev. Genet. 2004, 5: 101-113. 10.1038/nrg1272. Martinez-Antonio A, Janga SC, Thieffry D: Functional organisation of Escherichia coli transcriptional regulatory network. J. Mol. Biol. 2008, 381: 238-247. 10.1016/j.jmb.2008.05.054. Tagkopoulos I, Liu YC, Tavazoie S: Predictive behavior within microbial genetic networks. Science. 2008, 320: 1313-7. 10.1126/science.1154456. Amir M, Romano G, Groisman B, Yona A, Dekel E, Kupiec M, Dahan O, Pikpel Y: Adaptive prediction of environmental changes by microorganisms. Nature. 2009, 460: 220-225. 10.1038/nature08112. Thomas R: Boolean formalization of genetic control circuits. J. Theor. Biol. 1973, 42: 563-585. 10.1016/0022-5193(73)90247-6. Lagomarsino M, Jona P, Bassetti B, Isambert H: Hierarchy and feedback in the evolution of the Escherichia coli transcription network. Proc. Natl. Acad. Sci. USA. 2007, 104: 5516-5520. 10.1073/pnas.0609023104. Alon U: Network motifs: theory and experimental approaches. Nat. Rev. Genet. 2007, 8: 450-461. 10.1038/nrg2102. Moreno-Hagelsieb G, Latimer K: Choosing BLAST options for batter detection of orthologs as reciprocal best hits. Bioinformatics. 2008, 319-24. 24 Watts D, Strogatz S: Collective dynamics of 'small-world' networks. Nature. 1998, 393: 440-442. 10.1038/30918. Shen-Orr S, Milo R, Mangan S, Alon U: Network motifs in the transcriptional regulation network of Escherichia coli. Nature Genet. 2002, 31: 64-68. 10.1038/ng881. Doyle J, Csete M: Motifs, control, and stability. PLoS Biol. 2005, 3 (11): e392-10.1371/journal.pbio.0030392. Prill RJ, Iglesias PA, Levchenko A: Dynamic properties of network motifs contribute to biological network organization. PLoS Biol. 2005, 3 (11): e343-10.1371/journal.pbio.0030343. Mangan S, Zaslaver A, Alon U: The coherent feedforward loop serves as a signsensitive delay element in transcription networks. J. Mol. Biol. 2003, 334: 197-204. 10.1016/j.jmb.2003.09.049. Balázsi G, Barabási AL, Oltvai ZN: Topological units of environmental signal processing in the transcriptional regulatory network of Escherichia coli. Proc. Natl. Acad. Sci. USA. 2005, 102: 7841-7846. 10.1073/pnas.0500365102. Mangan S, Alon U: Structure and function of the feed-forward loop network motif. Proc. Natl. Acad. Sci. USA. 2003, 100: 11980-11985. 10.1073/pnas.2133841100. Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U: Network Motifs: Simple building blocks of complex networks. Science. 2002, 298: 824-827. 10.1126/science.298.5594.824. Balazsa G, Babarasi A L, Oltvai ZN: Topological units of enviromental signal processing in the transcriptional regulatory network of Escherichia coli. Proc. Natl. Acad. Sci. USA. 2005, 102: 7841-7846. 10.1073/pnas.0500365102. Martinez-Antonio A, Collado-Vides J: Identifying global regulators in transcriptional regulatory networks in bacteria. Curr. Opin. Microbiol. 2003, 6: 482-489. 10.1016/j.mib.2003.09.002. Resendis-Antonio O, Freyre-González J, Menchaca-Méndez R, Gutiérrez-Ríos R, Martínez Antonio A, Ávila-Sánchez C, Collado-Vides J: Molecular analysis of the transcriptional regulatory network of Escherichia coli. Trends Genet. 2005, 21 (1): 16-20. 10.1016/j.tig.2004.11.010. Shannon P, Markiel A, Ozier O, Baliga N, Wang J, Ramage D, Amin N, Schwikowski B, Ideker T: Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003, 13: 2498-2504. 10.1101/gr.1239303.