Skip to main content
SpringerLink
Log in

Biological robustness in complex host-pathogen systems

  • Chapter
Systems Biological Approaches in Infectious Diseases

Part of the book series: Progress in Drug Research ((PDR,volume 64))

Abstract

Infectious diseases are still the number one killer of human beings. Even in developed countries, infectious diseases continue to be a major health threat. This article explores a conceptual framework for understanding infectious diseases in the context of the complex dynamics between microbe and host, and explores theoretical strategies for anti-infectives. The central pillar of this conceptual framework is that biological robustness is a fundamental property of systems that is closely interlinked with the evolution of symbiotic host-pathogen systems. There are specific architectural features of such robust yet evolvable systems and interpretable trade-offs between robustness, fragility, resource demands, and performance. This concept applies equally to both microbes and host. Pathogens have evolved to exploit the host using various strategies as well as effective escape mechanisms. Modular pathogenicity islands (PAI) derived from horizontal gene transfer, highly variable surface molecules, and a range of other countermeasures enhance the robustness of a pathogen against attacks from the host immune system. The host has likewise evolved complex defensive mechanisms to protect itself against pathogenic threats, but the host immune system includes several trade-offs that can be exploited by pathogens and induces undesirable inflammatory reactions. Due to the complexity of the dynamics emerging from the interactions of multiple microbes and a host, effective counter-measures require an in-depth understanding of system dynamics as well as detailed molecular mechanisms of the processes that are involved.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kitano H (2004) Biological robustness. Nat Rev Genet 5(11): 826–837

    Article  PubMed  CAS  Google Scholar 

  2. Stelling J, Sauer U, Szallasi Z, Doyle FJ 3rd, Doyle J (2004) Robustness of cellular functions. Cell 118(6): 675–685

    Article  PubMed  CAS  Google Scholar 

  3. Alon U, Surette MG, Barkai N, Leibler S (1999) Robustness in bacterial chemotaxis. Nature 397(6715): 168–171

    Article  PubMed  CAS  Google Scholar 

  4. Barkai N, Leibler S (1997) Robustness in simple biochemical networks. Nature 387(6636): 913–917

    Article  PubMed  CAS  Google Scholar 

  5. Yi TM, Huang Y, Simon MI, Doyle J (2000) Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proc Natl Acad Sci USA 97(9): 4649–4653

    Article  PubMed  CAS  Google Scholar 

  6. von Dassow G, Meir E, Munro EM, Odell GM (2000) The segment polarity network is a robust developmental module. Nature 406(6792): 188–192

    Article  Google Scholar 

  7. Ingolia NT (2004) Topology and robustness in the Drosophila segment polarity network. PLoS Biol 2(6): E123

    Article  PubMed  CAS  Google Scholar 

  8. Little JW, Shepley DP, Wert DW (1999) Robustness of a gene regulatory circuit. Embo J 18(15): 4299–4307

    Article  PubMed  CAS  Google Scholar 

  9. Yachi S, Loreau M (1999) Biodiversity and ecosystem productivity in a fluctuating environment: the insurance hypothesis. Proc Natl Acad Sci USA 96(4): 1463–1468

    Article  PubMed  CAS  Google Scholar 

  10. Wagner GP, Altenberg L (1996) Complex adaptations and the evolution of evolvability. Evolution 50(3): 967–976

    Article  Google Scholar 

  11. Rutherford SL (2003) Between genotype and phenotype: protein chaperones and evolvability. Nat Rev Genet 4(4): 263–274

    Article  PubMed  CAS  Google Scholar 

  12. de Visser J, Hermission J, Wagner GP, Meyers L, Bagheri-Chaichian H, Blanchard J, Chao L, Cheverud J, Elena S, Fontana W et al (2003) Evolution and detection of genetics robustness. Evolution 57(9): 1959–1972

    Article  PubMed  Google Scholar 

  13. Gerhart J, Kirschner M (1997) Cells, embryos, and evolution: toward a cellular and developmental understanding of phenotypic variation and evolutionary adaptability. Blackwell Science, Malden, Massachusetts, USA

    Google Scholar 

  14. Kirschner M, Gerhart J (1998) Evolvability. Proc Natl Acad Sci USA 95(15): 8420–8427

    Article  PubMed  CAS  Google Scholar 

  15. Kitano H (2004) Cancer as a robust system: implications for anticancer therapy. Nat Rev Cancer 4(3): 227–235

    Article  PubMed  CAS  Google Scholar 

  16. Kitano H (2003) Cancer robustness: tumour tactics. Nature 426(6963): 125

    Article  PubMed  CAS  Google Scholar 

  17. Kitano H, Oda K, Kimura T, Matsuoka Y, Csete M, Doyle J, Muramatsu M (2004) Metabolic syndrome and robustness tradeoffs. Diabetes 53Suppl 3: S6–S15

    PubMed  CAS  Google Scholar 

  18. Tyson JJ, Chen K, Novak B (2001) Network dynamics and cell physiology. Nat Rev Mol Cell Biol 2(12): 908–916

    Article  PubMed  CAS  Google Scholar 

  19. Ferrell JE Jr (2002) Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14(2): 140–148

    Article  PubMed  CAS  Google Scholar 

  20. Chen KC, Calzone L, Csikasz-Nagy A, Cross FR, Novak B, Tyson JJ (2004) Integrative analysis of cell cycle control in budding yeast. Mol Biol Cell 15(8): 3841–3862

    Article  PubMed  CAS  Google Scholar 

  21. Agrawal AA (2001) Phenotypic plasticity in the interactions and evolution of species. Science 294(5541): 321–326

    Article  PubMed  CAS  Google Scholar 

  22. Schlichting C, Pigliucci M (1998) Phenotypic evolution: a reaction norm perspective. Sinauer Associates, Inc., Sunderland, MA, USA

    Google Scholar 

  23. Eldar A, Dorfman R, Weiss D, Ashe H, Shilo BZ, Barkai N (2002) Robustness of the BMP morphogen gradient in Drosophila embryonic patterning. Nature 419(6904): 304–308

    Article  PubMed  CAS  Google Scholar 

  24. Meir E, von Dassow G, Munro E, Odell GM (2002) Robustness, flexibility, and the role of lateral inhibition in the neurogenic network. Curr Biol 12(10): 778–786

    Article  PubMed  CAS  Google Scholar 

  25. Schlosser G, Wagner G (eds) (2004) Modularity in development and evolution. The University of Chicago Press, Chicago, USA

    Google Scholar 

  26. Rutherford SL, Lindquist S (1998) Hsp90 as a capacitor for morphological evolution. Nature 396(6709): 336–342

    Article  PubMed  CAS  Google Scholar 

  27. Queitsch C, Sangster TA, Lindquist S (2002) Hsp90 as a capacitor of phenotypic variation. Nature 417(6889): 618–624

    Article  PubMed  CAS  Google Scholar 

  28. Siegal ML, Bergman A (2002) Waddington’s canalization revisited: developmental stability and evolution. Proc Natl Acad Sci USA 99(16): 10528–10532

    Article  PubMed  CAS  Google Scholar 

  29. Waddington CH (1957) The strategy of the genes: a discussion of some aspects of theoretical biology. Macmillan, New York, USA

    Google Scholar 

  30. Lahav G, Rosenfeld N, Sigal A, Geva-Zatorsky N, Levine AJ, Elowitz MB, Alon U (2004) Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat Genet 36(2): 147–150

    Article  PubMed  CAS  Google Scholar 

  31. Csete ME, Doyle J (2004) Bow ties, metabolism and disease. Trends Biotechnol 22(9): 446–450

    Article  PubMed  CAS  Google Scholar 

  32. Carlson JM, Doyle J (1999) Highly optimized tolerance: a mechanism for power laws in designed systems. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 60(2 Pt A): 1412–1427

    PubMed  CAS  Google Scholar 

  33. Carlson JM, Doyle J (2002) Complexity and robustness. Proc Natl Acad Sci USA 99Suppl 1: 2538–2545

    Article  PubMed  Google Scholar 

  34. Csete ME, Doyle JC (2002) Reverse engineering of biological complexity. Science 295(5560): 1664–1669

    Article  PubMed  CAS  Google Scholar 

  35. Bak P, Tang C, Wiesenfeld K (1988) Self-organized criticality. Physical Review A 38(1): 364–374

    Article  PubMed  Google Scholar 

  36. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5(2): 101–113

    Article  PubMed  CAS  Google Scholar 

  37. Lamport L, Shostak R, Pease M (1982) The Byzantine generals problem. ACM Transactions on Programming Language and Systems 4(3): 382–401

    Article  Google Scholar 

  38. Ogawa M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, Sasakawa C (2005) Escape of intracellular Shigella from autophagy. Science 307(5710): 727–731

    Article  PubMed  CAS  Google Scholar 

  39. Hersh D, Monack DM, Smith MR, Ghori N, Falkow S, Zychlinsky A (1999) The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1. Proc Natl Acad Sci USA 96(5): 2396–2401

    Article  PubMed  CAS  Google Scholar 

  40. Waterman SR, Holden DW (2003) Functions and effectors of the Salmonella pathogenicity island 2 type III secretion system. Cell Microbiol 5(8): 501–511

    Article  PubMed  CAS  Google Scholar 

  41. Cossart P, Pizarro-Cerda J, Lecuit M (2003) Invasion of mammalian cells by Listeria monocytogenes: functional mimicry to subvert cellular functions. Trends Cell Biol 13(1): 23–31

    Article  PubMed  CAS  Google Scholar 

  42. Hacker J, Kaper JB (2000) Pathogenicity islands and the evolution of microbes. Annu Rev Microbiol 54: 641–679

    Article  PubMed  CAS  Google Scholar 

  43. Groisman EA, Ochman H (1996) Pathogenicity islands: bacterial evolution in quantum leaps. Cell 87(5): 791–794

    Article  PubMed  CAS  Google Scholar 

  44. Waldor MK, Mekalanos JJ (1996) Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272(5270): 1910–1914

    Article  PubMed  CAS  Google Scholar 

  45. Merrell DS, Falkow S (2004) Frontal and stealth attack strategies in microbial pathogenesis. Nature 430(6996): 250–256

    Article  PubMed  CAS  Google Scholar 

  46. Dubois ME, Demick KP, Mansfield JM (2005) Trypanosomes expressing a mosaic variant surface glycoprotein coat escape early detection by the immune system. Infect Immun 73(5): 2690–2697

    Article  PubMed  CAS  Google Scholar 

  47. Blaser MJ (2005) An endangered species in the stomach. Sci Am 292(2): 38–45

    Article  PubMed  Google Scholar 

  48. Umehara S, Higashi H, Ohnishi N, Asaka M, Hatakeyama M (2003) Effects of Helicobacter pylori CagA protein on the growth and survival of B lymphocytes, the origin of MALT lymphoma. Oncogene 22(51): 8337–8342

    Article  PubMed  CAS  Google Scholar 

  49. McCune JM (2001) The dynamics of CD4+ T-cell depletion in HIV disease. Nature 410(6831): 974–979

    Article  PubMed  CAS  Google Scholar 

  50. McMichael AJ, Rowland-Jones SL (2001) Cellular immune responses to HIV. Nature 410(6831): 980–987

    Article  PubMed  CAS  Google Scholar 

  51. Larder BA, Kemp SD (1989) Multiple mutations in HIV-1 reverse transcriptase confer high-level resistance to zidovudine (AZT). Science 246(4934): 1155–1158

    Article  PubMed  CAS  Google Scholar 

  52. Tisdale M, Kemp SD, Parry NR, Larder BA (1993) Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3′-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc Natl Acad Sci USA 90(12): 5653–5656

    Article  PubMed  CAS  Google Scholar 

  53. Larder BA, Kemp SD, Harrigan PR (1995) Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 269(5224): 696–699

    Article  PubMed  CAS  Google Scholar 

  54. Dropulic B, Hermankova M, Pitha PM (1996) A conditionally replicating HIV-1 vector interferes with wild-type HIV-1 replication and spread. Proc Natl Acad Sci USA 93(20): 11103–11108

    Article  PubMed  CAS  Google Scholar 

  55. Weinberger LS, Schaffer DV, Arkin AP (2003) Theoretical design of a gene therapy to prevent AIDS but not human immunodeficiency virus type 1 infection. J Virol 77(18): 10028–10036

    Article  PubMed  CAS  Google Scholar 

  56. Mautino MR, Morgan RA (2002) Gene therapy of HIV-1 infection using lentiviral vectors expressing anti-HIV-1 genes. AIDS Patient Care STDS 16(1): 11–26

    Article  PubMed  Google Scholar 

  57. Kitano H, Oda K (2006) Robustness trade-offs and host-microbial symbiosis in the immune system. Mol Sys Biol msb4100039-E1

    Google Scholar 

  58. Oda K, Kitano H (2006) A comprehensive molecular interaction map of Toll-like receptor signaling network. Mol Sys Biol msb4100057

    Google Scholar 

  59. Gilroy DW, Lawrence T, Perretti M, Rossi AG (2004) Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov 3(5): 401–416

    Article  PubMed  CAS  Google Scholar 

  60. Nathan C (2002) Points of control in inflammation. Nature 420(6917): 846–852

    Article  PubMed  CAS  Google Scholar 

  61. O’Shea JJ, Ma A, Lipsky P (2002) Cytokines and autoimmunity. Nat Rev Immunol 2(1): 37–45

    Article  PubMed  CAS  Google Scholar 

  62. Conn CA, McClellan JL, Maassab HF, Smitka CW, Majde JA, Kluger MJ (1995) Cytokines and the acute phase response to influenza virus in mice. Am J Physiol 268(1 Pt 2): R78–84

    PubMed  CAS  Google Scholar 

  63. Hennet T, Ziltener HJ, Frei K, Peterhans E (1992) A kinetic study of immune mediators in the lungs of mice infected with influenza A virus. J Immunol 149(3): 932–939

    PubMed  CAS  Google Scholar 

  64. Wyde PR, Wilson MR, Cate TR (1982) Interferon production by leukocytes infiltrating the lungs of mice during primary influenza virus infection. Infect Immun 38(3): 1249–1255

    PubMed  CAS  Google Scholar 

  65. Oda T, Akaike T, Hamamoto T, Suzuki F, Hirano T, Maeda H (1989) Oxygen radicals in influenza-induced pathogenesis and treatment with pyran polymer-conjugated SOD. Science 244(4907): 974–976

    Article  PubMed  CAS  Google Scholar 

  66. Ikemoto K, Pollard RB, Fukumoto T, Morimatsu M, Suzuki F (1995) Small amounts of exogenous IL-4 increase the severity of encephalitis induced in mice by the intranasal infection of herpes simplex virus type 1. J Immunol 155(3): 1326–1333

    PubMed  CAS  Google Scholar 

  67. Matsumori A, Shioi T, Yamada T, Matsui S, Sasayama S (1994) Vesnarinone, a new inotropic agent, inhibits cytokine production by stimulated human blood from patients with heart failure. Circulation 89(3): 955–958

    PubMed  CAS  Google Scholar 

  68. Matsui S, Matsumori A, Matoba Y, Uchida A, Sasayama S (1994) Treatment of virus-induced myocardial injury with a novel immunomodulating agent, vesnarinone. Suppression of natural killer cell activity and tumor necrosis factoralpha production. J Clin Invest 94(3): 1212–1217

    Article  PubMed  CAS  Google Scholar 

  69. Muto Y, Nouri-Aria KT, Meager A, Alexander GJ, Eddleston AL, Williams R (1988) Enhanced tumour necrosis factor and interleukin-1 in fulminant hepatic failure. Lancet 2(8602): 72–74

    Article  PubMed  CAS  Google Scholar 

  70. Wakabayashi G, Gelfand JA, Burke JF, Thompson RC, Dinarello CA (1991) A specific receptor antagonist for interleukin 1 prevents Escherichia coli-induced shock in rabbits. Faseb J 5(3): 338–343

    PubMed  CAS  Google Scholar 

  71. Csete M, Doyle J (2004) Bow ties, metabolism and disease. Trends Biotechnol 22(9): 446–450

    Article  PubMed  CAS  Google Scholar 

  72. Rudensky A, Preston-Hurlburt P, Hong SC, Barlow A, Janeway CA Jr (1991) Sequence analysis of peptides bound to MHC class II molecules. Nature 353(6345): 622–627

    Article  PubMed  CAS  Google Scholar 

  73. Brown JH, Jardetzky TS, Gorga JC, Stern LJ, Urban RG, Strominger JL, Wiley DC (1993) Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364(6432): 33–39

    Article  PubMed  CAS  Google Scholar 

  74. Yewdell JW, Bennink JR (2001) Cut and trim: generating MHC class I peptide ligands. Curr Opin Immunol 13(1): 13–18

    Article  PubMed  CAS  Google Scholar 

  75. Maeda S, Hsu LC, Liu H, Bankston LA, Iimura M, Kagnoff MF, Eckmann L, Karin M (2005) Nod2 mutation in Crohn’s disease potentiates NF-kappaB activity and IL-1beta processing. Science 307(5710): 734–738

    Article  PubMed  CAS  Google Scholar 

  76. Kobayashi KS, Chamaillard M, Ogura Y, Henegariu O, Inohara N, Nunez G, Flavell RA (2005) Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307(5710): 731–734

    Article  PubMed  CAS  Google Scholar 

  77. Tiveljung A, Soderholm JD, Olaison G, Jonasson J, Monstein HJ (1999) Presence of eubacteria in biopsies from Crohn’s disease inflammatory lesions as determined by 16S rRNA gene-based PCR. J Med Microbiol 48(3): 263–268

    PubMed  CAS  Google Scholar 

  78. Baum H, Davies H, Peakman M (1996) Molecular mimicry in the MHC: hidden clues to autoimmunity? Immunol Today 17(2): 64–70

    Article  PubMed  CAS  Google Scholar 

  79. Eriksson U, Ricci R, Hunziker L, Kurrer MO, Oudit GY, Watts TH, Sonderegger I, Bachmaier K, Kopf M, Penninger JM (2003) Dendritic cell-induced autoimmune heart failure requires cooperation between adaptive and innate immunity. Nat Med 9(12): 1484–1490

    Article  PubMed  CAS  Google Scholar 

  80. von Herrath MG, Fujinami RS, Whitton JL (2003) Microorganisms and autoimmunity: making the barren field fertile? Nat Rev Microbiol 1(2): 151–157

    Article  CAS  Google Scholar 

  81. Saikku P, Leinonen M, Mattila K, Ekman MR, Nieminen MS, Makela PH, Huttunen JK, Valtonen V (1988) Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 2(8618): 983–986

    Article  PubMed  CAS  Google Scholar 

  82. Campbell LA, Kuo CC (2004) Chlamydia pneumoniae — an infectious risk factor for atherosclerosis? Nat Rev Microbiol 2(1): 23–32

    Article  PubMed  CAS  Google Scholar 

  83. Haranaga S, Yamaguchi H, Friedman H, Izumi S, Yamamoto Y (2001) Chlamydia pneumoniae infects and multiplies in lymphocytes in vitro. Infect Immun 69(12): 7753–7759

    Article  PubMed  CAS  Google Scholar 

  84. Wick G, Perschinka H, Xu Q (1999) Autoimmunity and atherosclerosis. Am Heart J 138(5 Pt 2): S444–449

    Article  PubMed  CAS  Google Scholar 

  85. Bachmaier K, Neu N, de la Maza LM, Pal S, Hessel A, Penninger JM (1999) Chlamydia infections and heart disease linked through antigenic mimicry. Science 283(5406): 1335–1339

    Article  PubMed  CAS  Google Scholar 

  86. Xu J, Gordon JI (2003) Inaugural article: Honor thy symbionts. Proc Natl Acad Sci USA 100(18): 10452–10459

    Article  PubMed  CAS  Google Scholar 

  87. Savage DC (1977) Microbial ecology of the gastrointestinal tract. Annu Rev Microbiol 31: 107–133

    Article  PubMed  CAS  Google Scholar 

  88. Hooper LV, Midtvedt T, Gordon JI (2002) How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 22: 283–307

    Article  PubMed  CAS  Google Scholar 

  89. Macpherson AJ, Hunziker L, McCoy K, Lamarre A (2001) IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms. Microbes Infect 3(12): 1021–1035

    Article  PubMed  CAS  Google Scholar 

  90. Macpherson AJ, Martinic MM, Harris N (2002) The functions of mucosal T cells in containing the indigenous commensal flora of the intestine. Cell Mol Life Sci 59(12): 2088–2096

    Article  PubMed  CAS  Google Scholar 

  91. Stappenbeck TS, Hooper LV, Gordon JI (2002) Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci USA 99(24): 15451–15455

    Article  PubMed  CAS  Google Scholar 

  92. Kitano H, Oda K (2006) Self-extending symbiosis: a mechanism for increasing robustness through evolution. Biological Theory 1(1): 61–66

    Article  Google Scholar 

  93. Ushijima T, Ozaki Y (1988) Factors influencing potent antagonistic effects of Escherichia coli and Bacteroides ovatus on Staphylococcus aureus in anaerobic continuous flow cultures. Can J Microbiol 34(5): 645–650

    Article  PubMed  CAS  Google Scholar 

  94. Ushijima T, Ozaki Y (1986) Potent antagonism of Escherichia coli, Bacteroides ovatus, Fusobacterium varium, and Enterococcus faecalis, alone or in combination, for enteropathogens in anaerobic continuous flow cultures. J Med Microbiol 22(2): 157–163

    Article  PubMed  CAS  Google Scholar 

  95. Madsen K, Cornish A, Soper P, McKaigney C, Jijon H, Yachimec C, Doyle J, Jewell L, De Simone C (2001) Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology 121(3): 580–591

    Article  PubMed  CAS  Google Scholar 

  96. Sartor RB (2005) Probiotic therapy of intestinal inflammation and infections. Curr Opin Gastroenterol 21(1): 44–50

    PubMed  Google Scholar 

  97. Bergogne-Berezin E (2000) Treatment and prevention of antibiotic associated diarrhea. Int J Antimicrob Agents 16(4): 521–526

    Article  PubMed  CAS  Google Scholar 

  98. Cardinale BJ, Palmer MA, Collins SL (2002) Species diversity enhances ecosystem functioning through interspecific facilitation. Nature 415(6870): 426–429

    Article  PubMed  CAS  Google Scholar 

  99. Roberts MS, Garland JL, Mills AL (2004) Microbial astronauts: assembling microbial communities for advanced life support systems. Microb Ecol 47(2): 137–149

    Article  PubMed  CAS  Google Scholar 

  100. Ott SJ, Musfeldt M, Wenderoth DF, Hampe J, Brant O, Folsch UR, Timmis KN, Schreiber S (2004) Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 53(5): 685–693

    Article  PubMed  CAS  Google Scholar 

  101. Sartor RB (2003) Targeting enteric bacteria in treatment of inflammatory bowel diseases: why, how, and when. Curr Opin Gastroenterol 19(4): 358–365

    Article  PubMed  Google Scholar 

  102. Swidsinski A, Ladhoff A, Pernthaler A, Swidsinski S, Loening-Baucke V, Ortner M, Weber J, Hoffmann U, Schreiber S, Dietel M et al (2002) Mucosal flora in inflammatory bowel disease. Gastroenterology 122(1): 44–54

    Article  PubMed  Google Scholar 

  103. Backhed F, Ley R, Sonnenburg J, Peterson D, Gordon JI (2005) Host-bacterial mutualism in the human intestine. Science 307: 1915–1920

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Systems Biology Institute, Suite 6A, M31 6-31-15 Jingumae, Shibuya, Tokyo, 150-0001, Japan

    Hiroaki Kitano

  2. Sony Computer Science Laboratories, Inc., 3-14-13 Higashi-Gotanda, Shinagawa, Tokyo, 141-0022, Japan

    Hiroaki Kitano

Authors
  1. Hiroaki Kitano
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Tuberculosis Research Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, MD, 20852, USA

    Helena I. Boshoff  & Clifton E. Barry III  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Birkhäuser Verlag

About this chapter

Cite this chapter

Kitano, H. (2007). Biological robustness in complex host-pathogen systems. In: Boshoff, H.I., Barry, C.E. (eds) Systems Biological Approaches in Infectious Diseases. Progress in Drug Research, vol 64. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-7567-6_10

Download citation

Publish with us

Policies and ethics

Search

Navigation