Abstract
Salmonella and Yersinia are two distantly related genera containing species with wide host-range specificity and pathogenic capacity. The metabolic complexity of these organisms facilitates robust lifestyles both outside of and within animal hosts. Using a pathogen-centric systems biology approach, we are combining a multi-omics (transcriptomics, proteomics, metabolomics) strategy to define properties of these pathogens under a variety of conditions including those that mimic the environments encountered during pathogenesis. These high-dimensional omics datasets are being integrated in selected ways to improve genome annotations, discover novel virulence-related factors, and model growth under infectious states. We will review the evolving technological approaches toward understanding complex microbial life through multi-omic measurements and integration, while highlighting some of our most recent successes in this area.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Adams MD (1996) Serial analysis of gene expression: ESTs get smaller. BioEssays 18(4):261–262
Anderson L, Seilhamer J (1997) A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 18(3–4):533–537
Ansong C, Purvine SO, Adkins JN, Lipton MS, Smith RD (2008a) Proteogenomics: needs and roles to be filled by proteomics in genome annotation. Brief Funct Genomic Proteomic 7(1):50–62
Ansong C, Tolic N, Purvine SO, Porwollik S, Jones M, Yoon H, Payne SH, Martin JL, Burnet MC, Monroe ME et al (2011) Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium. BMC Genomics 12:433
Ansong C, Yoon H, Norbeck AD, Gustin JK, McDermott JE, Mottaz HM, Rue J, Adkins JN, Heffron F, Smith RD (2008b) Proteomics analysis of the causative agent of typhoid fever. J Proteome Res 7(2):546–557
Ansong C, Yoon H, Porwollik S, Mottaz-Brewer H, Petritis BO, Jaitly N, Adkins JN, McClelland M, Heffron F, Smith RD (2009) Global systems-level analysis of Hfq and SmpB deletion mutants in Salmonella: implications for virulence and global protein translation. PLoS One 4(3):e4809
Armengaud J (2009) A perfect genome annotation is within reach with the proteomics and genomics alliance. Curr Opin Microbiol 12(3):292–300
Bonneau R (2008) Learning biological networks: from modules to dynamics. Nat Chem Biol 4(11):658–664
Bordbar A, Lewis NE, Schellenberger J, Palsson BO, Jamshidi N (2010) Insight into human alveolar macrophage and M. tuberculosis interactions via metabolic reconstructions. Mol Syst Biol 6:422
Brenner DJ (1978) Characterization and clinical identification of Enterobacteriaceae by DNA hybridization. Prog Clin Pathol 7:71–117
Brenner DJ, Falkow S (1971) Genetics of the Enterobacteriaceae. C. Molecular relationships among members of the Enterobacteriaceae. Adv Genet 16:81–118
Brenner DJ, Fanning GR, Johnson KE, Citarella RV, Falkow S (1969) Polynucleotide sequence relationships among members of Enterobacteriaceae. J Bacteriol 98(2):637–650
Brubaker RR (1991) Factors promoting acute and chronic diseases caused by yersiniae. Clin Microbiol Rev 4(3):309–324
Cascante M, Marin S (2008) Metabolomics and fluxomics approaches. Essays Biochem 45:67–81
Cavanaugh DC, Randall R (1959) The role of multiplication of Pasteurella pestis in mononuclear phagocytes in the pathogenesis of flea-borne plague. J Immunol 83:348–363
Charusanti P, Chauhan S, McAteer K, Lerman JA, Hyduke DR, Motin VL, Ansong C, Adkins JN, Palsson BO (2011) An experimentally-supported genome-scale metabolic network reconstruction for Yersinia pestis CO92. BMC Syst Biol 5:163
Coburn B, Grassl GA, Finlay BB (2007) Salmonella, the host and disease: a brief review. Immunol Cell Biol 85(2):112–118
Coombes BK, Wickham ME, Lowden MJ, Brown NF, Finlay BB (2005) Negative regulation of Salmonella pathogenicity island 2 is required for contextual control of virulence during typhoid. Proc Natl Acad Sci U S A 102(48):17460–17465
Cornelis GR (1998) The Yersinia deadly kiss. J Bacteriol 180(21):5495–5504
Cornelis GR (2002) Yersinia type III secretion: send in the effectors. J Cell Biol 158(3):401–408
de Groot A, Dulermo R, Ortet P, Blanchard L, Guerin P, Fernandez B, Vacherie B, Dossat C, Jolivet E, Siguier P et al (2009) Alliance of proteomics and genomics to unravel the specificities of Sahara bacterium Deinococcus deserti. PLoS Genet 5(3):e1000434
De Smet R, Marchal K (2010) Advantages and limitations of current network inference methods. Nat Rev Microbiol 8(10):717–729
Deiwick J, Nikolaus T, Erdogan S, Hensel M (1999) Environmental regulation of Salmonella pathogenicity island 2 gene expression. Mol Microbiol 31(6):1759–1773
Duarte NC, Becker SA, Jamshidi N, Thiele I, Mo ML, Vo TD, Srivas R, Palsson BO (2007) Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci U S A 104(6):1777–1782
Faith JJ, Hayete B, Thaden JT, Mogno I, Wierzbowski J, Cottarel G, Kasif S, Collins JJ, Gardner TS (2007) Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLoS Biol 5(1):e8
Feist AM, Herrgard MJ, Thiele I, Reed JL, Palsson BO (2009) Reconstruction of biochemical networks in microorganisms. Nat Rev Microbiol 7(2):129–143
Feist AM, Palsson BO (2008) The growing scope of applications of genome-scale metabolic reconstructions using Escherichia coli. Nat Biotechnol 26(6):659–667
Feist AM, Palsson BO (2010) The biomass objective function. Curr Opin Microbiol 13(3):344–349
Fields PI, Swanson RV, Haidaris CG, Heffron F (1986) Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc Natl Acad Sci U S A 83(14):5189–5193
Fukuto HS, Svetlanov A, Palmer LE, Karzai AW, Bliska JB (2010) Global gene expression profiling of Yersinia pestis replicating inside macrophages reveals the roles of a putative stress-induced operon in regulating type III secretion and intracellular cell division. Infect Immun 78(9):3700–3715
Glynn MK, Bopp C, Dewitt W, Dabney P, Mokhtar M, Angulo FJ (1998) Emergence of multidrug-resistant Salmonella enterica serotype typhimurium DT104 infections in the United States. N Engl J Med 338(19):1333–1338
Gygi SP, Corthals GL, Zhang Y, Rochon Y, Aebersold R (2000) Evaluation of two-dimensional gel electrophoresis-based proteome analysis technology. Proc Natl Acad Sci U S A 97(17):9390–9395
Haynes PA, Gygi SP, Figeys D, Aebersold R (1998) Proteome analysis: biological assay or data archive? Electrophoresis 19(11):1862–1871
Herrgard MJ, Covert MW, Palsson BO (2004) Reconstruction of microbial transcriptional regulatory networks. Curr Opin Biotechnol 15(1):70–77
Hyduke DR, Palsson BO (2010) Towards genome-scale signalling network reconstructions. Nat Rev Genet 11(4):297–307
Jaffe JD, Berg HC, Church GM (2004) Proteogenomic mapping as a complementary method to perform genome annotation. Proteomics 4(1):59–77
Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006) Experimental and computational assessment of conditionally essential genes in Escherichia coli. J Bacteriol 188(23):8259–8271
Kueger S, Steinhauser D, Willmitzer L, Giavalisco P (2012) High-resolution plant metabolomics: from mass spectral features to metabolites and from whole-cell analysis to subcellular metabolite distributions. Plant J 70(1):39–50
Lerat E, Daubin V, Moran NA (2003) From gene trees to organismal phylogeny in prokaryotes: the case of the gamma-Proteobacteria. PLoS Biol 1(1):E19
Lewis NE, Cho BK, Knight EM, Palsson BO (2009) Gene expression profiling and the use of genome-scale in silico models of Escherichia coli for analysis: providing context for content. J Bacteriol 191(11):3437–3444
Ly M, Laremore TN, Linhardt RJ (2010) Proteoglycomics: recent progress and future challenges. OMICS 14(4):389–399
Margolin AA, Califano A (2007) Theory and limitations of genetic network inference from microarray data. Ann N Y Acad Sci 1115:51–72
Martin JA, Wang Z (2011) Next-generation transcriptome assembly. Nat Rev Genet 12(10):671–682
McDermott JE, Archuleta M, Thrall BD, Adkins JN, Waters KM (2011a) Controlling the response: predictive modeling of a highly central, pathogen-targeted core response module in macrophage activation. PLoS One 6(2):e14673
McDermott JE, Corrigan A, Peterson E, Oehmen C, Niemann G, Cambronne ED, Sharp D, Adkins JN, Samudrala R, Heffron F (2011b) Computational prediction of type III and IV secreted effectors in gram-negative bacteria. Infect Immun 79(1):23–32
McDermott JE, Taylor RC, Yoon H, Heffron F (2009) Bottlenecks and hubs in inferred networks are important for virulence in Salmonella typhimurium. J Comput Biol 16(2):169–180
Miao EA, Miller SI (2000) A conserved amino acid sequence directing intracellular type III secretion by Salmonella typhimurium. Proc Natl Acad Sci U S A 97(13):7539–7544
Nicholson JK, Lindon JC, Holmes E (1999) ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29(11):1181–1189
Niemann GS, Brown RN, Gustin JK, Stufkens A, Shaikh-Kidwai AS, Li J, McDermott JE, Brewer HM, Schepmoes A, Smith RD et al (2011) Discovery of novel secreted virulence factors from Salmonella enterica serovar Typhimurium by proteomic analysis of culture supernatants. Infect Immun 79(1):33–43
Oberhardt MA, Palsson BO, Papin JA (2009) Applications of genome-scale metabolic reconstructions. Mol Syst Biol 5:320
Oldiges M, Lutz S, Pflug S, Schroer K, Stein N, Wiendahl C (2007) Metabolomics: current state and evolving methodologies and tools. Appl Microbiol Biotechnol 76(3):495–511
Orth JD, Thiele I, Palsson BO (2010) What is flux balance analysis? Nat Biotechnol 28(3):245–248
Ozsolak F, Milos PM (2011) RNA sequencing: advances, challenges and opportunities. Nat Rev Genet 12(2):87–98
Palsson B (2004) Two-dimensional annotation of genomes. Nat Biotechnol 22(10):1218–1219
Palsson B, Zengler K (2010) The challenges of integrating multi-omic data sets. Nat Chem Biol 6(11):787–789
Payne SH, Huang ST, Pieper R (2010) A proteogenomic update to Yersinia: enhancing genome annotation. BMC Genomics 11:460
Perry RD, Fetherston JD (1997) Yersinia pestis–etiologic agent of plague. Clin Microbiol Rev 10(1):35–66
Reed JL, Famili I, Thiele I, Palsson BO (2006) Towards multidimensional genome annotation. Nat Rev Genet 7(2):130–141
Samudrala R, Heffron F, McDermott JE (2009) Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems. PLoS Pathog 5(4):e1000375
Schellenberger J, Park JO, Conrad TM, Palsson BO (2010) BiGG: a biochemical genetic and genomic knowledgebase of large scale metabolic reconstructions. BMC Bioinformatics 11:213
Schrimpe-Rutledge AC, Jones MB, Chauhan S, Purvine SO, Sanford JA, Monroe ME, Brewer HM, Payne SH, Ansong C, Frank BC et al (2012) Comparative omics-driven genome annotation refinement: application across Yersiniae. PLoS One 7(3):e33903
Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, Chen W, Selbach M (2011) Global quantification of mammalian gene expression control. Nature 473(7347):337–342
Segre D, Vitkup D, Church GM (2002) Analysis of optimality in natural and perturbed metabolic networks. Proc Natl Acad Sci U S A 99(23):15112–15117
Sharp PM (1991) Determinants of DNA sequence divergence between Escherichia coli and Salmonella typhimurium: codon usage, map position, and concerted evolution. J Mol Evol 33(1):23–33
Sittka A, Lucchini S, Papenfort K, Sharma CM, Rolle K, Binnewies TT, Hinton JC, Vogel J (2008) Deep sequencing analysis of small noncoding RNA and mRNA targets of the global post-transcriptional regulator Hfq. PLoS Genet 4(8):e1000163
Straley SC, Harmon PA (1984a) Growth in mouse peritoneal macrophages of Yersinia pestis lacking established virulence determinants. Infect Immun 45(3):649–654
Straley SC, Harmon PA (1984b) Yersinia pestis grows within phagolysosomes in mouse peritoneal macrophages. Infect Immun 45(3):655–659
Straley SC, Plano GV, Skrzypek E, Haddix PL, Fields KA (1993) Regulation by Ca2+ in the Yersinia low-Ca2+ response. Mol Microbiol 8(6):1005–1010
Thiele I, Hyduke DR, Steeb B, Fankam G, Allen DK, Bazzani S, Charusanti P, Chen FC, Fleming RM, Hsiung CA et al (2011) A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella Typhimurium LT2. BMC Syst Biol 5:8
Thiele I, Jamshidi N, Fleming RM, Palsson BO (2009) Genome-scale reconstruction of Escherichia coli’s transcriptional and translational machinery: a knowledge base, its mathematical formulation, and its functional characterization. PLoS Comput Biol 5(3):e1000312
Thiele I, Palsson BO (2010) A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc 5(1):93–121
Velculescu VE, Zhang L, Zhou W, Vogelstein J, Basrai MA, Bassett DE Jr, Hieter P, Vogelstein B, Kinzler KW (1997) Characterization of the yeast transcriptome. Cell 88(2):243–251
Vidal SM, Malo D, Marquis JF, Gros P (2008) Forward genetic dissection of immunity to infection in the mouse. Annu Rev Immunol 26:81–132
Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10(1):57–63
Welkos SL, Davis KM, Pitt LM, Worsham PL, Freidlander AM (1995) Studies on the contribution of the F1 capsule-associated plasmid pFra to the virulence of Yersinia pestis. Contrib Microbiol Immunol 13:299–305
Welkos SL, Friedlander AM, Davis KJ (1997) Studies on the role of plasminogen activator in systemic infection by virulent Yersinia pestis strain C092. Microb Pathog 23(4):211–223
White AP, Weljie AM, Apel D, Zhang P, Shaykhutdinov R, Vogel HJ, Surette MG (2010) A global metabolic shift is linked to Salmonella multicellular development. PLoS One 5(7):e11814
Worsham PL, Stein MP, Welkos SL (1995) Construction of defined F1 negative mutants of virulent Yersinia pestis. Contrib Microbiol Immunol 13:325–328
Wright JC, Sugden D, Francis-McIntyre S, Riba-Garcia I, Gaskell SJ, Grigoriev IV, Baker SE, Beynon RJ, Hubbard SJ (2009) Exploiting proteomic data for genome annotation and gene model validation in Aspergillus niger. BMC Genomics 10:61
Yoon H, Ansong C, McDermott JE, Gritsenko M, Smith RD, Heffron F, Adkins JN (2011) Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella. BMC Syst Biol 5:100
Zhang W, Li F, Nie L (2010) Integrating multiple ‘omics’ analysis for microbial biology: application and methodologies. Microbiology 156(Pt 2):287–301
Acknowledgments
Research described was supported by the National Institute of Allergy and Infectious Diseases NIH/DHHS through Interagency agreement Y1-AI-8401. Proteomics and metabolomics capabilities were developed under support from the US Department of Energy (DOE) Office of Biological and Environmental Research (BER) and the NIH grants 5P41RR018522-10 and the National Institute of General Medical Sciences grant (8 P41 GM103493-10), and work was performed in the Environmental Molecular Sciences Laboratory, a DOE-BER national scientific user facility at Pacific Northwest National Laboratory (PNNL). PNNL is a multiprogram national laboratory operated by Battelle Memorial Institute for the DOE under contract DE-AC05-76RLO 1830.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Ansong, C. et al. (2012). Studying Salmonellae and Yersiniae Host–Pathogen Interactions Using Integrated ‘Omics and Modeling. In: Katze, M. (eds) Systems Biology. Current Topics in Microbiology and Immunology, vol 363. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2012_247
Download citation
DOI: https://doi.org/10.1007/82_2012_247
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-33098-8
Online ISBN: 978-3-642-33099-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)