The Origin of the Bacterial Immune Response

  • Jesús Martínez-Borra
  • Segundo González
  • Carlos López-LarreaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 738)


Bacteriophages are probably the oldest viruses, having appeared early during bacterial evolution. Therefore, bacteria and bacteriophages have a long history of co-evolution in which bacteria have developed multiple resistance mechanisms against bacteriophages. These mechanisms, that are very diverse and are in constant evolution, allow the survival of the bacteria. Bacteriophages have adapted to bacterial defense systems, devised strategies to evade these anti-phage mechanisms and restored their infective capacity. In this chapter, we review the bacterial strategies that hinder the phage infection as well as the counter-defense mechanisms developed


Quorum Sense Phage Infection Lytic Cycle CRISPR Locus CRISPR System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hoskisson PA, Smith MCM. Hypervariation and phase variation in the bacteriophage ‘resistome’. Curr Opin Microbiol 2007; 10:396–400.PubMedCrossRefGoogle Scholar
  2. 2.
    Labrie SJ, Samson JE, Moineau S. Bacteriophage resistance mechanism. Nat Rev Microbiol 2010; 5:317–327.CrossRefGoogle Scholar
  3. 3.
    McAuliffe O, Ross RP, Fitzgerald GF. The new phage biology: from genomics to applications. In: McGrath S and van Sinderen D, eds. Bacteriophage Genetics and Molecular Biology. Norfolk: Caister Academic Press 2007: 1–42.Google Scholar
  4. 4.
    Ackermann H-W. Bacteriophage obserations and evolution. Res Microbiol 2003; 154:245–251.PubMedCrossRefGoogle Scholar
  5. 5.
    Cuttman B, Raya R, Kutter E. Basic phage biology. In: Kutter E and Sulakvelidze A, eds. Bacteriophages. Biology and Applications. Boca Raton: CRC Press 2005: 29–66.Google Scholar
  6. 6.
    Casjens S. Prophages and bacterial genomics: what have we learned so far? Mol Microbiol 2003; 49:277–300.PubMedCrossRefGoogle Scholar
  7. 7.
    Liu M, Deora R, Doulatov SR et al. Reverse transcriptase-meditated tropism switching in Bordetella bacteriophage. Science 2002; 295:2091–2094.PubMedCrossRefGoogle Scholar
  8. 8.
    Doulatov S, Hodes A, Dai L et al. Tropism switching in Bordetella bacteriophage defines a family of diversity-generating retroelements. Nature 2004; 431:473–481.CrossRefGoogle Scholar
  9. 9.
    Destoumieux-Garzond, Duquesne S, Peduzzi J et al. The iron-siderophore transporter FhuA is the receptor for the antimicrobial peptide microcin J25: role of the microcin Val11-Pro16 β-hairpin region in the recognition mechanism. Biochem J 2005; 389:869–876.CrossRefGoogle Scholar
  10. 10.
    Vicent PA, Morero RD. The structure and biological aspects of peptide antibiotic microcin J25. Curr Med Chem 2009; 16:538–549.CrossRefGoogle Scholar
  11. 11.
    Riede I, Eschbach M-L. Evidence that TraT interacts with OmpA of Escherichia coli. FEBS Lett 1986; 205:241–245.PubMedCrossRefGoogle Scholar
  12. 12.
    Bruttin A, Desiere F, Lucchini S et al. Characterization of the lysogeny DNA module from teteperate Streptococcus thermophilus bacteriophage φSfi21. Virology 1997; 233:136–148.PubMedCrossRefGoogle Scholar
  13. 13.
    McGrath S, Fitzgerald GF, van Sinderen D. Identification and characterization of phage-resistance genes in temperate lactococcal bacteriophages. Mol Microbiol 2002; 43:509–520.PubMedCrossRefGoogle Scholar
  14. 14.
    Lopez D, Vlamakis H, Kolter R. Biofilms. Cold Spring Harb Perspect Biol 2010; 2:a000398.CrossRefGoogle Scholar
  15. 15.
    Sutherland IW, Hughes KA, Skillman LC et al. The interaction of phage and biofilms. FEMS Microbiol Lett 2004; 232:1–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Tait K, Sutherland IW. The efficacy of bacteriophages as a method of biofilm eradication. Biofouling 2002; 18:305–310.CrossRefGoogle Scholar
  17. 17.
    Richard AH, Gilbert P, High NJ et al. Bacterial coaggregation: an integral process in the development of multi-species biofilms. Trends microbial 2003; 11:94–100.CrossRefGoogle Scholar
  18. 18.
    Ghosh D, Roy K, Williamson KE et al. Acyl-homoserine lactones can induce virus production in lysogenic bacteria: an alternative paradigm for prophage induction. Appl Environ Microbiol 2009; 75:7142–7152.PubMedCrossRefGoogle Scholar
  19. 19.
    Wilson GG. Restriction and modification systems. Annu Rev Genet 1991; 25:585–627.PubMedCrossRefGoogle Scholar
  20. 20.
    Price C, Bickle TA. A possible role for DNA restriction in bacterial evolution. Microbiol Sci 1986; 3:296–299.PubMedGoogle Scholar
  21. 21.
    Tock MR, Dryden DTF. The biology of restriction and anti-restriction. Curr Opin Microbiol 2005; 8:466–472.PubMedCrossRefGoogle Scholar
  22. 22.
    Roberts RJ et al. A nomenclature for restriction enzymes, DNA methytransferases, homing endonucelases and their genes. Nucleic Acids Res 2003; 31:1805–1812.PubMedCrossRefGoogle Scholar
  23. 23.
    Kruger DH, Barcak GJ, Smith HO. Abolition of DNA recognition site resistance to the restriction endonuclease EcoRII. Biomed Biochim Acta 1988; 47:K1–K5.PubMedGoogle Scholar
  24. 24.
    Blair CL, Black LW. A type IV modification dependent restriction nuclease that targets glucosylated hydroxymethyl cytosine modified DNAs. J Mol Biol 2007; 366:768–778.CrossRefGoogle Scholar
  25. 25.
    Blair CL, Rifat D, Black LW. Exclusion of glucosyl-hydroxymethylcytosine DNA containing bacteriophages is overcome by the injected protein inhibitor IPI*. J Mol Biol 2007; 366:779–789.CrossRefGoogle Scholar
  26. 26.
    Bedford D, Laity C, Buttner MJ. Two genes involved in the phase-variable phi C31 resistance mechanism of Streptomyces coelicolor A3(2). J Bacteriol 1995; 177:4681–4689.PubMedGoogle Scholar
  27. 27.
    Sumby P, Smit MCM. Phase variation in the phage growth limitation system of Streptomices coelicor A3(2). J Bacteriol 2003; 4558–4563.Google Scholar
  28. 28.
    Studier FW, Novva NR. SAMase gene of bacteriophage T3 is responsible for overcoming host restriction. J Virol 1976; 19:136–145.PubMedGoogle Scholar
  29. 29.
    Walkinshaw MD, Taylor P, Sturrock SS et al. Structure of OCR from bacteriophage T7, a protein that mimics B-form DNA. Mol Cell 2002; 9:18–94.CrossRefGoogle Scholar
  30. 30.
    Barrangou R, Fremaux C, Deveau H et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 2007; 315:1709–1712.PubMedCrossRefGoogle Scholar
  31. 31.
    Andersson AF, Banfield JF. Virus population dynamics and acquired virus resistance in natural microbial communities. Science 2008; 320:1047–1050.PubMedCrossRefGoogle Scholar
  32. 32.
    Ishino Y, Shinagawa H, Makino K et al. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli and identification of the gene product. J Bacteriol 1987; 169:5429–5433.PubMedGoogle Scholar
  33. 33.
    Jansen R, Embden JD, Gaastra W et al. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 2002; 43:1565–1575.PubMedCrossRefGoogle Scholar
  34. 34.
    Marraffini LA, Sontheimer EJ. CRISPR interference: RNA-directed adaptive immunity in bacteria and archaea. Nat Rev Genet 2010; 11:181–190.PubMedCrossRefGoogle Scholar
  35. 35.
    Bult CJ, White O, Olsen GJ et al. Complete genome sequence of the methanogenic archaeon, Methanococcus jannaschii. Science 1996; 273:1058–1073.PubMedCrossRefGoogle Scholar
  36. 36.
    Grissa I, Vergnaud G, Pourcel C. The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats. BMC Bioinformatics 2007; 8:172.PubMedCrossRefGoogle Scholar
  37. 37.
    Kunin V, Sorek R, Hugenholtz P. Evolutionary conservation of sequence and secondary structures in CRISPR repeats. Genome Biol 2007; 8:R61.PubMedCrossRefGoogle Scholar
  38. 38.
    Mojica FJ, Díez-Villaseñor C, García-Martínez J et al. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol 2005; 60:174–182.PubMedCrossRefGoogle Scholar
  39. 39.
    Lillestøl RK, Shah SA, Brügger K et al. CRISPR families of the crenarchaeal genus Sulfolobus: bidirectional transcription and dynamic properties. Mol Microbiol 2009; 72:259–272.PubMedCrossRefGoogle Scholar
  40. 40.
    Hale C, Kleppe K, Terns RM et al. Prokaryotic silencing (psi)RNAs in Pyrococcus furiosus. RNA 2008; 14:2572–2579.PubMedCrossRefGoogle Scholar
  41. 41.
    Haft DH, Selengut J, Mongodin EF et al. A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes. PLoS Comput Biol 2005; 1:e60.PubMedCrossRefGoogle Scholar
  42. 42.
    Wiedenheft B, Zhou K, Jinek M et al. Structural basis for DNase activity of a conserved protein implicated in CRISPR-mediated genome defense. Structure 2009; 17:904–912.PubMedCrossRefGoogle Scholar
  43. 43.
    Beloglazova N, Brown G, Zimmerman MD et al. A novel family of sequence-specific endoribonucleases associated with the clustered regularly interspaced short palindromic repeats. J Biol Chem 2008; 283:20361–20371.PubMedCrossRefGoogle Scholar
  44. 44.
    Brouns SJ, Jore MM, Lundgren M et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 2008; 321:960–964.PubMedCrossRefGoogle Scholar
  45. 45.
    Carte J, Wang R, Li H et al. Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes. Genes Dev 2008; 22:3489–3496.PubMedCrossRefGoogle Scholar
  46. 46.
    Makarova KS, Grishin NV, Shabalina SA et al. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi and hypothetical mechanisms of action. Biol Direct 2006; 1:7.PubMedCrossRefGoogle Scholar
  47. 47.
    Marraffini LA, Sontheimer EJ. Self versus nonself discrimination during CRISPR RNA-directed immunity. Nature 2010; 463:568–571.PubMedCrossRefGoogle Scholar
  48. 48.
    Snyder L. Phage-exclusion enzymes: a bonanza of biochemical and cell biology reagent? Mol Microbiol 1995; 15:415–420.PubMedCrossRefGoogle Scholar
  49. 49.
    Slavcev RA, Hayes S. Over-expression of rexA nullifies T4rII exclusion in Escherichia coli K(γ) lysogens. Can J Microbiol 2004; 50:133–136.PubMedCrossRefGoogle Scholar
  50. 50.
    Amitsur M, Levitz R, Kaufmann G. Bacteriophage T4 anticodon nuclease, polynucleotide kinase and RNA ligase reprocess the host lysine tRNA. EMBO J 1987; 6:2499–2503.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Jesús Martínez-Borra
    • 1
  • Segundo González
    • 2
  • Carlos López-Larrea
    • 1
    • 3
    Email author
  1. 1.Immunology DepartmentHospital Universitario Central de AsturiasOviedoSpain
  2. 2.Department of Functional BiologyUniversity of Oviedo, IUOPAOviedoSpain
  3. 3.Fundación Renal “Iñigo Álvarez de Toledo”Hospital Universitario Central de AsturiasMadridSpain

Personalised recommendations