Advertisement

Journal of Microbiology

, Volume 52, Issue 3, pp 243–258 | Cite as

Phage lysis: Three steps, three choices, one outcome

  • Ryland Young
Review

Abstract

The lysis of bacterial hosts by double-strand DNA bacteriophages, once thought to reflect merely the accumulation of sufficient lysozyme activity during the infection cycle, has been revealed to recently been revealed to be a carefully regulated and temporally scheduled process. For phages of Gramnegative hosts, there are three steps, corresponding to subversion of each of the three layers of the cell envelope: inner membrane, peptidoglycan, and outer membrane. The pathway is controlled at the level of the cytoplasmic membrane. In canonical lysis, a phage encoded protein, the holin, accumulates harmlessly in the cytoplasmic membrane until triggering at an allele-specific time to form micron-scale holes. This allows the soluble endolysin to escape from the cytoplasm to degrade the peptidoglycan. Recently a parallel pathway has been elucidated in which a different type of holin, the pinholin, which, instead of triggering to form large holes, triggers to form small, heptameric channels that serve to depolarize the membrane. Pinholins are associated with SAR endolysins, which accumulate in the periplasm as inactive, membrane-tethered enzymes. Pinholin triggering collapses the proton motive force, allowing the SAR endolysins to refold to an active form and attack the peptidoglycan. Surprisingly, a third step, the disruption of the outer membrane is also required. This is usually achieved by a spanin complex, consisting of a small outer membrane lipoprotein and an integral cytoplasmic membrane protein, designated as o-spanin and i-spanin, respectively. Without spanin function, lysis is blocked and progeny virions are trapped in dead spherical cells, suggesting that the outer membrane has considerable tensile strength. In addition to two-component spanins, there are some single-component spanins, or u-spanins, that have an N-terminal outer-membrane lipoprotein signal and a C-terminal transmembrane domain. A possible mechanism for spanin function to disrupt the outer membrane is to catalyze fusion of the inner and outer membranes.

Keywords

lysis holin anti-holin endolysin SAR endolysin i-spanin o-spanin u-spanin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adhya, S., Sen, A., and Mitra, S. 1971. The role of gene S. In Hershey, A.D. (ed.), The Bacteriophage Lambda, Vol. 1, pp. 743–746. Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y., USA.Google Scholar
  2. Altman, E., Altman, R.K., Garrett, J.M., Grimaila, R.J., and Young, R. 1983. S gene product: identification and membrane localization of a lysis control protein. J. Bacteriol. 155, 1130–1137.PubMedCentralPubMedGoogle Scholar
  3. Altman, E., Young, K., Garrett, J., Altman, R., and Young, R. 1985. Subcellular localization of lethal lysis proteins of bacteriophages λ and ΦX174. J. Virol. 53, 1008–1011.PubMedCentralPubMedGoogle Scholar
  4. Atkins, J.F., Steitz, J.A., Anderson, C.W., and Model, P. 1979. Binding of mammalian ribosomes to MS2 phage RNA reveals an overlapping gene encoding a lysis function. Cell 18, 247–256.PubMedCrossRefGoogle Scholar
  5. Barenboim, M., Chang, C.Y., dib Hajj, F., and Young, R. 1999. Characterization of the dual start motif of a class II holin gene. Mol. Microbiol. 32, 715–727.PubMedCrossRefGoogle Scholar
  6. Bartel, P.L., Roecklein, J.A., SenGupta, D., and Fields, S. 1996. A protein linkage map of Escherichia coli bacteriophage T7. Nat. Genet. 12, 72–77.PubMedCrossRefGoogle Scholar
  7. Bayer, M.E. 1968. Areas of adhesion between wall and membrane of Escherichia coli J. Gen. Microbiol. 53, 395–404.CrossRefGoogle Scholar
  8. Benzer, S., Cairns, J., Stent, G.S., and Watson, J.D. 1966. Adventures in the rII region. In Phage and the Origins of Molecular Biology, pp. 157–165. Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, NY, USA.Google Scholar
  9. Berry, J., Savva, C., Holzenburg, A., and Young, R. 2010. The lambda spanin components Rz and Rz1 undergo tertiary and quaternary rearrangements upon complex formation. Protein Sci. 19, 1967–1977.Google Scholar
  10. Berry, J., Summer, E.J., Struck, D.K., and Young, R. 2008. The final step in the phage infection cycle: the Rz and Rz1 lysis proteins link the inner and outer membranes. Mol. Microbiol. 70, 341–351.PubMedCrossRefGoogle Scholar
  11. Berry, J.D., Rajaure, M., Pang, T., and Young, R. 2012. The spanin complex is essential for lambda lysis. J. Bacteriol. 194, 5667–5674.PubMedCentralPubMedCrossRefGoogle Scholar
  12. Berry, J.D., Rajaure, M., and Young, R. 2013. Spanin function requires subunit homodimerization through intermolecular disulfide bonds. Mol. Microbiol. 88, 35–47.PubMedCrossRefGoogle Scholar
  13. Bienkowska-Szewczyk, K., Lipinska, B., and Taylor, A. 1981. The R gene product of bacteriophage λ is the murein transglycosylase. Mol. Gen. Genet. 184, 111–114.PubMedCrossRefGoogle Scholar
  14. Bienkowska-Szewczyk, K. and Taylor, A. 1980. Murein transglycosylase from phage λ lysate: purification and properties. Biochim. Biophys. Acta 615, 489–496.PubMedCrossRefGoogle Scholar
  15. Bläsi, U., Chang, C.Y., Zagotta, M.T., Nam, K., and Young, R. 1990. The lethal λ S gene encodes its own inhibitor. EMBO J. 9, 981–989.PubMedCentralPubMedGoogle Scholar
  16. Bläsi, U., Nam, K., Hartz, D., Gold, L., and Young, R. 1989. Dual translational initiation sites control function of the λ S gene. EMBO J. 8, 3501–3510.PubMedCentralPubMedGoogle Scholar
  17. Bonovich, M.T. and Young, R. 1991. Dual start motif in two lambdoid S genes unrelated to lambda S. J. Bacteriol. 173, 2897–2905.PubMedCentralPubMedGoogle Scholar
  18. Bryl, K., Kedzierska, S., Laskowska, M., and Taylor, A. 2000. Membrane fusion by proline-rich Rz1 lipoprotein, the bacteriophage lambda Rz1 gene product. Eur. J. Biochem. 267, 794–799.PubMedCrossRefGoogle Scholar
  19. Bull, J.J., Pfennig, D.W., and Wang, I.N. 2004. Genetic details, optimization and phage life histories. Trends Ecol. Evol. 19, 76–82.PubMedCrossRefGoogle Scholar
  20. Cairns, J., Stent, G.S., and Watson, J.D. 2000. Phage and the origins of molecular biology. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA.Google Scholar
  21. Casjens, S.R., Eppler, K., Parr, R., and Poteete, A.R. 1989. Nucleotide sequence of the bacteriophage P22 gene 19 to 3 region: Identification of a new gene required for lysis. Virol. 171, 588–598.Google Scholar
  22. Catalão, M.J., Gil, F., Moniz-Pereira, J., Sao-Jose, C., and Pimentel, M. 2013. Diversity in bacterial lysis systems: bacteriophages show the way. FEMS Microbiol. Rev. 37, 554–571.PubMedCrossRefGoogle Scholar
  23. Chang, C.Y., Nam, K., Bläsi, U., and Young, R. 1993. Synthesis of two bacteriophage λ S proteins in an in vivo system. Gene 133, 9–16.PubMedCrossRefGoogle Scholar
  24. Chang, C.Y., Nam, K., and Young, R. 1995. S gene expression and the timing of lysis by bacteriophage λ. J. Bacteriol. 177, 3283–3294.PubMedCentralPubMedGoogle Scholar
  25. Dewey, J.S., Savva, C.G., White, R.L., Vitha, S., Holzenburg, A., and Young, R. 2010. Micron-scale holes terminate the phage infection cycle. Proc. Natl. Acad. Sci. USA 107, 2219–2223.PubMedCentralPubMedCrossRefGoogle Scholar
  26. Fleming, A. 1922. On a remarkable bacteriolytic element found in tissues and secretions. Proc. R. Soc. Lond. B. 93, 306–317.CrossRefGoogle Scholar
  27. Fletcher, G., Wulff, J.L., and Earhart, C.F. 1974. Localization of membrane protein synthesized after infection with bacteriophage T4. J. Virol. 13, 73–80.PubMedCentralPubMedGoogle Scholar
  28. Garrett, J., Fusselman, R., Hise, J., Chiou, L., Smith-Grillo, D., Schulz, R., and Young, R. 1981. Cell lysis by induction of cloned lambda lysis genes. Mol. Gen. Genet. 182, 326–331.PubMedCrossRefGoogle Scholar
  29. Garrett, J.M. and Young, R. 1982. Lethal action of bacteriophage lambda S gene. J. Virol. 44, 886–892.PubMedCentralPubMedGoogle Scholar
  30. Gründling, A., Bläsi, U., and Young, R. 2000a. Genetic and biochemical analysis of dimer and oligomer interactions of the lambda S holin. J. Bacteriol. 182, 6082–6090.PubMedCentralPubMedCrossRefGoogle Scholar
  31. Gründling, A., Manson, M.D., and Young, R. 2001. Holins kill without warning. Proc. Natl. Acad. Sci. USA 98, 9348–9352.PubMedCentralPubMedCrossRefGoogle Scholar
  32. Gründling, A., Smith, D.L., Bläsi, U., and Young, R. 2000b. Dimerization between the holin and holin inhibitor of phage lambda. J. Bacteriol. 182, 6075–6081.PubMedCentralPubMedCrossRefGoogle Scholar
  33. Graschopf, A. and Bläsi, U. 1999. Molecular function of the dual-start motif in the λ S holin. Mol. Microbiol. 33, 569–582.PubMedCrossRefGoogle Scholar
  34. Hanych, B., Kedzierska, S., Walderich, B., and Taylor, A. 1993a. Molecular cloning, overexpression of Rz lysis gene of phage λ, and subcellular localization of its protein product. In de Pedro, M.A., Hoeltje, J.V., and Loeffelhardt, W. (eds.), Bacterial growth and lysis, pp. 269–276. Plenum Press, New York and London.CrossRefGoogle Scholar
  35. Hanych, B., Kedzierska, S., Walderich, B., Uznanski, B., and Taylor, A. 1993b. Expression of the Rz gene and the overlapping Rz1 reading frame present at the right end of the bacteriophage lambda genome. Gene 129, 1–8.PubMedCrossRefGoogle Scholar
  36. Ito, K. and Inaba, K. 2008. The disulfide bond formation (Dsb) system. Curr. Opin. Struct. Biol. 18, 450–458.PubMedCrossRefGoogle Scholar
  37. Jahn, R. and Scheller, R.H. 2006. SNAREs-engines for membrane fusion. Nat. Rev. Mol. Cell Biol. 7, 631–643.PubMedCrossRefGoogle Scholar
  38. Johnson-Boaz, R., Chang, C.Y., and Young, R. 1994. A dominant mutation in the bacteriophage lambda S gene causes premature lysis and an absolute defective plating phenotype. Mol. Microbiol. 13, 495–504.PubMedCrossRefGoogle Scholar
  39. Juncker, A.S., Willenbrock, H., von Heijne, G., Brunak, S., Nielsen, H., and Krogh, A. 2003. Prediction of lipoprotein signal peptides in Gram-negative bacteria. Protein Sci. 12, 1652–1662.PubMedCentralPubMedCrossRefGoogle Scholar
  40. Kedzierska, S., Wawrzynow, A., and Taylor, A. 1996. The Rz1 gene product of bacteriophage lambda is a lipoprotein localized in the outer membrane of Escherichia coli. Gene 168, 1–8.PubMedCrossRefGoogle Scholar
  41. Kellenberger, E. 1990. The ‘Bayer bridges’ confronted with results from improved electron microscopy methods. Mol. Microbiol. 4, 697–705.PubMedCrossRefGoogle Scholar
  42. Krupovič, M., Cvirkaitė-Krupovič, V., and Bamford, D.H. 2008. Identification and functional analysis of the Rz/Rz1-like accessory lysis genes in the membrane-containing bacteriophage PRD1. Mol. Microbiol. 68, 492–503.PubMedCrossRefGoogle Scholar
  43. Kucharczyk, K., Laskowska, E., and Taylor, A. 1991. Response of Escherichia coli cell membranes to induction of lambda cl857 prophage by heat shock. Mol. Microbiol. 5, 2935–2945.PubMedCrossRefGoogle Scholar
  44. Kuty, G.F., Xu, M., Struck, D.K., Summer, E.J., and Young, R. 2010. Regulation of a phage endolysin by disulfide caging. J. Bacteriol. 192, 5682–5687.PubMedCentralPubMedCrossRefGoogle Scholar
  45. Matthews, B.W., Remington, S.J., Grutter, M.G., and Anderson, W.F. 1981. Relation between hen egg white lysozyme and bacteriophage T4 lysozyme: evolutionary implications. J. Mol. Biol. 147, 545–558.PubMedCrossRefGoogle Scholar
  46. Moussa, S.H., Kuznetsov, V., Tran, T.A., Sacchettini, J.C., and Young, R. 2012. Protein determinants of phage T4 lysis inhibition. Protein Sci. 21, 571–582.PubMedCentralPubMedCrossRefGoogle Scholar
  47. Okuda, S. and Tokuda, H. 2011. Lipoprotein sorting in bacteria. Annu. Rev. Microbiol. 65, 239–259.PubMedCrossRefGoogle Scholar
  48. Osborn, M.J. and Munson, R. 1974. Separation of the inner (cytoplasmic) and outer membranes of Gram-negative bacteria. Methods Enzymol. 31, 642–653.PubMedCrossRefGoogle Scholar
  49. Pang, T., Park, T., and Young, R. 2010a. Mapping the pinhole formation pathway of S21. Mol. Microbiol. 78, 710–719.PubMedCentralPubMedCrossRefGoogle Scholar
  50. Pang, T., Park, T., and Young, R. 2010b. Mutational analysis of the S21 pinholin. Mol. Microbiol. 76, 68–77.PubMedCentralPubMedCrossRefGoogle Scholar
  51. Pang, T., Savva, C.G., Fleming, K.G., Struck, D.K., and Young, R. 2009. Structure of the lethal phage pinhole. Proc. Natl. Acad. Sci. USA 106, 18966–18971.PubMedCentralPubMedCrossRefGoogle Scholar
  52. Park, T., Struck, D.K., Dankenbring, C.A., and Young, R. 2007. The pinholin of lambdoid phage 21: control of lysis by membrane depolarization. J. Bacteriol. 189, 9135–9139.PubMedCentralPubMedCrossRefGoogle Scholar
  53. Park, T., Struck, D.K., Deaton, J.F., and Young, R. 2006. Topological dynamics of holins in programmed bacterial lysis. Proc. Natl. Acad. Sci. USA 103, 19713–19718.PubMedCentralPubMedCrossRefGoogle Scholar
  54. Raab, R., Neal, G., Garrett, J., Grimaila, R., Fusselman, R., and Young, R. 1986. Mutational analysis of bacteriophage lambda lysis gene S. J. Bacteriol. 167, 1035–1042.PubMedCentralPubMedGoogle Scholar
  55. Raab, R., Neal, G., Sohaskey, C., Smith, J., and Young, R. 1988. Dominance in lambda S mutations and evidence for translational control. J. Mol. Biol. 199, 95–105.PubMedCrossRefGoogle Scholar
  56. Ramanculov, E.R. and Young, R. 2001a. An ancient player unmasked: T4 rI encodes a t-specific antiholin. Mol. Microbiol. 41, 575–583.PubMedCrossRefGoogle Scholar
  57. Ramanculov, E.R. and Young, R. 2001b. Functional analysis of the T4 t holin in a lambda context. Mol. Genet. Genomics 265, 345–353.PubMedCrossRefGoogle Scholar
  58. Ramanculov, E.R. and Young, R. 2001c. Genetic analysis of the T4 holin: timing and topology. Gene 265, 25–36.PubMedCrossRefGoogle Scholar
  59. Reddy, B.L. and Saier, M.H.Jr. 2013. Topological and phylogenetic analyses of bacterial holin families and superfamilies. Biochim. Biophys. Acta. 1828, 2654–2671.PubMedCrossRefGoogle Scholar
  60. Risselada, H.J. and Grubmuller, H. 2012. How SNARE molecules mediate membrane fusion: recent insights from molecular simulations. Curr. Opin. Struct. Biol. 22, 187–196.PubMedCrossRefGoogle Scholar
  61. Rydman, P.S. and Bamford, D.H. 2003. Identification and mutational analysis of bacteriophage PRD1 holin protein P35. J. Bacteriol. 185, 3795–3803.PubMedCentralPubMedCrossRefGoogle Scholar
  62. Sanger, F., Air, G.M., Barrell, B.G., Brown, N.L., Coulson, A.R., Fiddes, J.C., Hutchison, C.A., III, Slocombe, P.M., and Smith, M. 1977. Nucleotide sequence of bacteriophage ΦX174 DNA. Nature 265, 687–695.PubMedCrossRefGoogle Scholar
  63. São-José, C., Parreira, R., and Santos, M.A. 2003. Triggering of hostcell lysis by double-stranded DNA bacteriophages: Fundamental concepts, recent developments and emerging applications. Recent Res. Devel. Bacteriol. 1, 103–130.Google Scholar
  64. São-José, C., Parreira, R., Vieira, G., and Santos, M.A. 2000. The N-terminal region of the Oenococcus oeni bacteriophage fOg44 lysin behaves as a bona fide signal peptide in Escherichia coli and as a cis-inhibitory element, preventing lytic activity on oenococcal cells. J. Bacteriol. 182, 5823–5831.PubMedCentralPubMedCrossRefGoogle Scholar
  65. Savva, C.G., Dewey, J.S., Moussa, S.H., To, K.H., Holzenburg, A., and Young, R. 2014. Stable micron-scale holes are a general feature of canonical holins. Mol. Microbiol. 91, 57–65.PubMedCrossRefGoogle Scholar
  66. Schmidt, C., Velleman, M., and Arber, W. 1996. Three functions of bacteriophage P1 involved in cell lysis. J. Bacteriol. 178, 1099–1104.PubMedCentralPubMedGoogle Scholar
  67. Steiner, M. and Bläsi, U. 1993. Charged amino-terminal amino acids affect the lethal capacity of lambda lysis proteins S107 and S105. Mol. Microbiol. 8, 525–533.PubMedCrossRefGoogle Scholar
  68. Summer, E.J., Berry, J., Tran, T.A., Niu, L., Struck, D.K., and Young, R. 2007. Rz / Rz1 lysis gene equivalents in phages of Gram-negative hosts. J. Mol. Biol. 373, 1098–1112.PubMedCrossRefGoogle Scholar
  69. Sun, Q., Kuty, G.F., Arockiasamy, A., Xu, M., Young, R., and Sacchettini, J.C. 2009. Regulation of a muralytic enzyme by dynamic membrane topology. Nat. Struct. Mol. Biol. 16, 1192–1194.PubMedCentralPubMedCrossRefGoogle Scholar
  70. Taylor, A. 1971. Endopeptidase activity of phage λ endolysin. Nat. New Biol. 234, 144–145.PubMedCrossRefGoogle Scholar
  71. Taylor, A., Benedik, M., and Campbell, A. 1983. Location of the Rz gene in bacteriophage lambda. Gene 26, 159–163.PubMedCrossRefGoogle Scholar
  72. Taylor, A. and Gorazdowska, M. 1974. Conversion of murein to non-reducing fragments by enzymes from phage lambda and Vi II lysates. Biochim. Biophys. Acta. 342, 133–136.PubMedCrossRefGoogle Scholar
  73. Tran, T.A., Struck, D.K., and Young, R. 2007. The T4 RI antiholin has an N-terminal signal anchor release domain that targets it for degradation by DegP. J. Bacteriol. 189, 7618–7625.PubMedCentralPubMedCrossRefGoogle Scholar
  74. Tran, T.A.T., Struck, D.K., and Young, R. 2005. Periplasmic domains define holin-antiholin interactions in T4 lysis inhibition. J. Bacteriol. 187, 6631–6640.PubMedCentralPubMedCrossRefGoogle Scholar
  75. Walker, D.H. Jr., and Walker, J.T. 1975. Genetic studies of coliphage P1. I. Mapping by use of prophage deletions. J. Virol. 16, 525–534.PubMedCentralPubMedGoogle Scholar
  76. Wang, I.N. 2006. Lysis timing and bacteriophage fitness. Genetics 172, 17–26.PubMedCentralPubMedCrossRefGoogle Scholar
  77. Wang, I.N., Dykhuizen, D.E., and Slobodkin, L.B. 1996. The evolution of phage lysis timing. Evol. Ecol. 10, 545–558.CrossRefGoogle Scholar
  78. Watson, J.D., Hopkins, N.H., Roberts, J.W., Steitz, J.A., and Weiner, A.M. 1987. Molecular Biology of the Gene. Benjamin/Cummings Publishing Co., Inc., Menlo Park, CA, USA.Google Scholar
  79. White, R., Chiba, S., Pang, T., Dewey, J.S., Savva, C.G., Holzenburg, A., Pogliano, K., and Young, R. 2011. Holin triggering in real time. Proc. Natl. Acad. Sci. USA 108, 798–803.PubMedCentralPubMedCrossRefGoogle Scholar
  80. White, R., Tran, T.A., Dankenbring, C.A., Deaton, J., and Young, R. 2010. The N-terminal transmembrane domain of λ S is required for holin but not antiholin function. J. Bacteriol. 192, 725–733.PubMedCentralPubMedCrossRefGoogle Scholar
  81. Xu, M., Arulandu, A., Struck, D.K., Swanson, S., Sacchettini, J.C., and Young, R. 2005. Disulfide isomerization after membrane release of its SAR domain activates P1 lysozyme. Science 307, 113–117.PubMedCrossRefGoogle Scholar
  82. Xu, M., Struck, D.K., Deaton, J., Wang, I.N., and Young, R. 2004. The signal arrest-release (SAR) sequence mediates export and control of the phage P1 endolysin. Proc. Natl. Acad. Sci. USA 101, 6415–6420.PubMedCentralPubMedCrossRefGoogle Scholar
  83. Young, R. 1992. Bacteriophage lysis: mechanism and regulation. Microbiol. Rev. 56, 430–481.PubMedCentralPubMedGoogle Scholar
  84. Young, R. 2013. Phage lysis: do we have the hole story yet? Curr. Opin. Microbiol. 16, 790–797.PubMedCrossRefGoogle Scholar
  85. Young, R. and Wang, I.N. 2006. Phage lysis. In Calendar, R. (ed.), The Bacteriophages, pp. 104–126. Oxford University Press, Oxford, UK.Google Scholar
  86. Young, R., Way, S., Yin, J., and Syvanen, M. 1979. Transposition mutagenesis of bacteriophage lambda: a new gene affecting cell lysis. J. Mol. Biol. 132, 307–322.PubMedCrossRefGoogle Scholar
  87. Zagotta, M.T. and Wilson, D.B. 1990. Oligomerization of the bacteriophage lambda S protein in the inner membrane of Escherichia coli. J. Bacteriol. 172, 912–921.PubMedCentralPubMedGoogle Scholar
  88. Zhang, N. and Young, R. 1999. Complementation and characterization of the nested Rz and Rz1 reading frames in the genome of bacteriophage lambda. Mol. Gen. Genetics 262, 659–667.CrossRefGoogle Scholar
  89. Ziermann, R., Bartlett, B., Calendar, R., and Christie, G.E. 1994. Functions involved in bacteriophage P2-induced host cell lysis and identification of a new tail gene. J. Bacteriol. 176, 4974–4984.PubMedCentralPubMedGoogle Scholar

Copyright information

© The Microbiological Society of Korea and Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Center for Phage Technology, Department of Biochemistry and BiophysicsTexas A&M UniversityCollege StationUSA

Personalised recommendations