Abstract

The release of phage progeny from an infected bacterium is necessary for the spread of infection. Only helical phages are secreted from a cell without causing its destruction. The release of remaining phages is correlated with bacterial lysis and death. Thus, the understanding of phage lytic functions is crucial for their use in the fight with bacterial pathogens. Bacteriophages with small RNA or DNA genomes encode single proteins which are called amurins and cause lysis by the inhibition of cell wall synthesis. Bacteriophages of double-stranded DNA genomes, which dominate in the environment, encode enzymes that are called endolysins and contribute to lysis by the cleavage of cell wall peptydoglycan. Endolysins that do not contain signal sequences cannot pass the cytoplasmic membrane by themselves. Their access to peptidoglycan is provided by membrane proteins – holins, which can form in the membrane large pores, that are called “holes”. Some endolysins do not require holins for their transport, owing to the presence of the so called SAR sequence at their N-terminus. It enables their transport through the membrane by the bacterial sec system. However, it is not cleaved off, and thus these endolysins remain trapped in the membrane in an inactive form. Their release, which is correlated with the activation, occurs as a result of membrane depolarization and depends on proteins that are called pinholins. Pinholins form in membrane pores that are too small for the passage of endolysins but sufficient for membrane depolarization. Proteins that are called antiholins regulate the timing of lysis, through the blockage of holins action until the end of phage morphogenesis. Additionally, newly identified lytic proteins, spanins, participate in the release of progeny phages from Gram-negative bacteria cells. They cause the destruction of outer cell membrane by its spanning with the cytoplasmic membrane. This is possible after the endolysin-mediated destruction of peptidoglycan, which separates both membranes, and ensures the fast completion of lysis.

References

• 1. Baker J.R., Liu C., Dong S., Pritchard D.G.: Endopeptidase andglycosidase activities of the bacteriophage B30 lysin. Appl. Environ.Microbiol., 2006; 72: 6825-6828
  Google Scholar
• 2. Barenboim M., Chang C.Y., dib Hajj F., Young R.: Characterizationof the dual start motif of a class II holin gene. Mol. Microbiol.,1999; 32: 715-727
  Google Scholar
• 3. Becker S.C., Dong S., Baker J.R., Foster-Frey J., Pritchard D.G., DonovanD.M.: LysK CHAP endopeptidase domain is required for lysisof live staphylococcal cells. FEMS Microbiol. Lett., 2009; 294: 52-60
  Google Scholar
• 4. Becker S.C., Foster-Frey J., Donovan D.M.: The phage K lytic enzymeLysK and lysostaphin act synergistically to kill MRSA. FEMSMicrobiol. Lett., 2008; 287: 185-191
  Google Scholar
• 5. Bernhardt T.G., Wang I.N., Struck D.K., Young R.: A protein antibioticin the phage Qβ virion: diversity in lysis targets. Science,2001; 292: 2326-2329
  Google Scholar
• 6. Bernhardt T.G., Wang I.N., Struck D.K, Young R.: Breaking free:“protein antibiotics” and phage lysis. Res. Microbiol., 2002; 153:493-501
  Google Scholar
• 7. Berry J., Rajaure M., Pang T., Young R.: The spanin complex is essentialfor lambda lysis. J. Bacteriol., 2012; 194: 5667-5674
  Google Scholar
• 8. Berry J.D., Rajaure M., Young R.: Spanin function requires subunithomodimerization through intermolecular disulfide bonds. Mol.Microbiol., 2013; 88: 35-47
  Google Scholar
• 9. Berry J., Summer E.J., Struck D.K., Young R.: The final step in thephage infection cycle: the Rz and Rz1 lysis proteins link the innerand outer membranes. Mol. Microbiol., 2008; 70: 341-351
  Google Scholar
• 10. Bonovich M.T., Young R.: Dual start motif in two lambdoid S genesunrelated to lambda S. J. Bacteriol., 1991; 173: 2897-2905
  Google Scholar
• 11. Borysowski J., Weber-Dąbrowska B., Górski A.: Bacteriophageendolysins as a novel class of antibacterial agents. Exp. Biol. Med.,2006; 231: 366-377
  Google Scholar
• 12. Briers Y., Lavigne R., Plessers P., Hertveldt K., Hanssens I., EngelborghsY., Volckaert G.: Stability analysis of the bacteriophagephiKMV lysin gp36C and its putative role during infection. Cell. Mol.Life Sci., 2006; 63: 1899-1905
  Google Scholar
• 13. Briers Y., Peeters L.M., Volckaert G., Lavigne R.: The lysis cassetteof bacteriophage фKMV encodes a signal-arrest-release endolysinand a pinholin. Bacteriophage, 2011; 1: 25-30
  Google Scholar
• 14. Briers Y., Schmelcher M., Loessner M.J., Hendrix J., EngelborghsY., Volckaert G., Lavigne R.: The high-affinity peptidoglycan bindingdomain of Pseudomonas phage endolysin KZ144. Biochem. Biophys.Res. Comm., 2009; 383: 187-191
  Google Scholar
• 15. Briers Y., Volckaert G., Cornelissen A., Lagaert S., Michiels C.W.,Hertveldt K., Lavigne R.: Muralytic activity and modular structureof the endolysins of Pseudomonas aeruginosa bacteriophages ϕKZ andEL. Mol. Microbiol., 2007; 65: 1334-1344
  Google Scholar
• 16. Caldentey J., Hänninen A.L., Bamford D.H.: Gene XV of bacteriophagePRD1 encodes a lytic enzyme with muramidase activity.Eur. J. Biochem., 1994; 225: 341-346
  Google Scholar
• 17. Chang C.Y., Nam K., Young R.: S gene expression and the timingof lysis by bacteriophage λ. J. Bacteriol., 1995; 177: 3283-3294
  Google Scholar
• 18. Dennehy J.J., Wang I.N.: Factors influencing lysis time stochasticityin bacteriophage λ. BMC Microbiol., 2011; 11: 174
  Google Scholar
• 19. Desmarais S.M., De Pedro M.A., Cava F., Huang K.C.: Peptidoglycanat its peaks: how chromatographic analyses can reveal bacterialcell wall structure and assembly. Mol. Microbiol., 2013; 89: 1-13
  Google Scholar
• 20. Dewey J.S., Savva C.G., White R.L., Vitha S., Holzenburg A., YoungR.: Micron-scale holes terminate the phage infection cycle. Proc.Natl. Acad. Sci. USA, 2010; 107: 2219-2223
  Google Scholar
• 21. Donovan D.M., Foster-Frey J.: LambdaSa2 prophage endolysinrequires Cpl-7-binding domains and amidase-5 domain for antimicrobiallysis of streptococci. FEMS Microbiol. Lett., 2008; 287: 22-33
  Google Scholar
• 22. Eugster M.R., Haug M.C., Huwiler S.G., Loessner M.J.: The cellwall binding domain of Listeria bacteriophage endolysin PlyP35 recognizesterminal GlcNAc residues in cell wall teichoic acid. Mol.Microbiol., 2011; 81: 1419-1432
  Google Scholar
• 23. Fenton M., Ross P., McAuliffe O., O’Mahony J., Coffey A.: Recombinantbacteriophage lysins as antibacterials. Bioeng. Bugs, 2010; 1: 9-16
  Google Scholar
• 24. Fischetti V.A.: Bacteriophage lytic enzymes: novel anti-infectives.Trends Microbiol., 2005; 13: 491-496
  Google Scholar
• 25. Foley S., Bruttin A., Brüssow H.: Widespread distribution ofa group I intron and its three deletion derivatives in the lysin gene ofStreptococcus thermophilus bacteriophages. J. Virol., 2000; 74: 611-618
  Google Scholar
• 26. Garcia P., Martin A.C., López R.: Bacteriophages of Streptococcuspneumoniae: a molecular approach. Microb. Drug Resist., 1997; 3: 165-176
  Google Scholar
• 27. Gründling A., Manson M.D., Young R.: Holins kill without warning.Proc. Natl. Acad. Sci. USA, 2001; 98: 9348-9352
  Google Scholar
• 28. Gründling A., Smith D.L., Bläsi U., Young R.: Dimerization betweenthe holin and holin inhibitor of phage λ. J. Bacteriol., 2000;182: 6075-6081
  Google Scholar
• 29. Guttman B., Raya P., Kutter E.: Basic phage biology. W: Bacteriophages:biology and application, red.: E.B. Kutter, A. Sulakvelidze,CRC Press, Boca Raton (FL), 2005; 29-66
  Google Scholar
• 30. Hermoso J.A., Garcia J.L., Garcia P.: Taking aim on bacterial pathogens:from phage therapy to enzybiotics. Curr. Opin. Microbiol.,2007; 10: 461-472
  Google Scholar
• 31. Jacob F., Fuerst C.R.: The mechanism of lysis by phage studiedwith defective lysogenic bacteria. J. Gen. Microbiol., 1958; 18: 518-526
  Google Scholar
• 32. Krupovič M., Bamford D.H.: Holin of bacteriophage lambda: structuralinsights into a membrane lesion. Mol. Microbiol., 2008; 69: 781-783
  Google Scholar
• 33. Kuty G.F., Xu M., Struck D.K., Summer E.J., Young R.: Regulationof a phage endolysin by disulfide caging. J. Bacteriol., 2010;192: 5682-5687
  Google Scholar
• 34. Lai M.J., Lin N.T., Hu A., Soo P.C., Chen L.K., Chen L.H., ChangK.C.: Antibacterial activity of Acinetobacter baumannii phage φAB2endolysin (LysAB2) against both gram-positive and gram-negativebacteria. Appl. Microbiol. Biotechnol., 2011; 90: 529-539
  Google Scholar
• 35. Lehnherr H., Hansen A.M., Ilyina T.: Penetration of the bacterialcell wall: a family of lytic transglycosylases in bacteriophages andconjugative plasmids. Mol. Microbiol., 1998; 30: 454-457
  Google Scholar
• 36. Loessner M.J.: Bacteriophage endolysins – current state of researchand applications. Curr. Opin. Microbiol., 2005; 8: 480-487
  Google Scholar
• 37. Loessner M.J., Kramer K., Ebel F., Scherer S.: C-terminal domainsof Listeria monocytogenes bacteriophage murein hydrolases determinespecific recognition and high-affinity binding to bacterial cell wallcarbohydrates. Mol. Microbiol., 2002; 44: 335-349
  Google Scholar
• 38. Loessner M.J., Wendlinger G., Scherer S.: Heterogeneous endolysinsin Listeria monocytogenes bacteriophages: a new class of enzymesand evidence for conserved holin genes within the siphoviral lysiscassettes. Mol. Microbiol., 1995; 16: 1231-1241
  Google Scholar
• 39. Lood R., Raz A., Molina H., Euler C.W., Fischetti V.A.: A highly activeand negatively charged Streptococcus pyogenes lysin with a rare D-alanyl–L-alanine endopeptidase activity protects mice against streptococcalbacteremia. Antimicrob. Agents Chemother., 2014; 58: 3073-3084
  Google Scholar
• 40. Łobocka M.B., Rose D.J., Plunkett G.3rd, Rusin M., Samojedny A.,Lehnherr H., Yarmolinsky M.B., Blattner F.R.: Genome of bacterophageP1. J. Bacteriol., 2004; 186: 7032-7068
  Google Scholar
• 41. Mosig G., Lin G.W., Franklin J., Fan W.H.: Functional relationshipsand structural determinants of two bacteriophage T4 lysozymes:a soluble (gene e) and a baseplate-associated (gene 5) protein. NewBiol., 1989; 1: 171-179
  Google Scholar
• 42. Navarre W.W., Ton-That H., Faull K.F., Schneewind O.: Multipleenzymatic activities of the murein hydrolase from staphylococcalphage φ11. Identification of a D-alanyl-glycine endopeptidase activity.J. Biol. Chem., 1999; 274: 15847-15856
  Google Scholar
• 43. Nelson D., Schuch R., Chahales P., Zhu S., Fischetti V.A.: PlyC:a multimeric bacteriophage lysin. Proc. Natl. Acad. Sci. USA, 2006;103: 10765-10770
  Google Scholar
• 44. Nelson D.C., Schmelcher M., Rodriguez-Rubio L., Klumpp J.,Pritchard D.G., Dong S., Donovan D.M.: Endolysins as antimicrobials.Adv. Virus Res., 2012; 83: 299-365
  Google Scholar
• 45. Pang T., Park T., Young R.: Mapping the pinhole formation pathwayof S21. Mol. Microbiol., 2010; 78: 710-719
  Google Scholar
• 46. Pang T., Park T., Young R.: Mutational analysis of the S21 pinholin.Mol. Microbiol., 2010; 76: 68-77
  Google Scholar
• 47. Pang T., Savva C.G., Fleming K.G., Struck D.K., Young R.: Structureof the lethal phage pinhole. Proc. Natl. Acad. Sci. USA, 2009;106: 18966-18971
  Google Scholar
• 48. Parisien A., Allain B., Zhang J., Mandeville R., Lan C.Q.: Novelalternatives to antibiotics: bacteriophages, bacterial cell wall hydrolases,and antimicrobial peptides. J. Appl. Microbiol., 2008; 104: 1-13
  Google Scholar
• 49. Park T., Struck D.K., Dankenbring C.A., Young R.: The pinholinof lambdoid phage 21: control of lysis by membrane depolarization.J. Bacteriol., 2007; 189: 9135-9139
  Google Scholar
• 50. Park T., Struck D.K., Deaton J.F., Young R.: Topological dynamicsof holins in programmed bacterial lysis. Proc. Natl. Acad. Sci. USA,2006; 103: 19713-19718
  Google Scholar
• 51. Payne K.M., Hatfull G.F.: Mycobacteriophage endolysins: diverseand modular enzymes with multiple catalytic activities. PLoS One,2012; 7: e34052
  Google Scholar
• 52. Pritchard D.G., Dong S., Baker J.R., Engler J.A.: The bifunctionalpeptidoglycan lysin of Streptococcus agalactiae bacteriophage B30.Microbiology, 2004; 150: 2079-2087
  Google Scholar
• 53. Pritchard D.G., Dong S., Kirk M.C., Cartee R.T., Baker J.R.: LambdaSa1and LambdaSa2 prophage lysins of Streptococcus agalactiae.Appl. Environ. Microbiol., 2007; 73: 7150-7154
  Google Scholar
• 54. Rashel M., Uchiyama J., Takemura I., Hoshiba H., Ujihara T., TakatsujiH., Honke K., Matsuzaki S.: Tail-associated structural proteingp61 of Staphylococcus aureus phage φMR11 has bifunctional lyticactivity. FEMS Microbiol. Lett., 2008; 284: 9-16
  Google Scholar
• 55. Reddy B.L., Saier M.H.Jr.: Topological and phylogenetic analysesof bacterial holin families and superfamilies. Biochim. Biophys.Acta, 2013; 1828: 2654-2671
  Google Scholar
• 56. Rice K.C., Bayles K.W.: Molecular control of bacterial death andlysis. Microbiol. Mol. Biol. Rev., 2008: 72: 85-109
  Google Scholar
• 57. Rydman P.S., Bamford D.H.: Identification and mutational analysisof bacteriophage PRD1 holin protein P35. J. Bacteriol., 2003;185: 3795-3803
  Google Scholar
• 58. Sao-Jose C., Nascrimento J.G., Parreira R., Santos M.A.: Releaseof progeny phages from infected cells. W: Bacteriophage Geneticsand Molecular Biology, Mc Grath S., van Sinderen D. (red.), CaisterAcademic Press, Norfolk, UK., 2007; 307-334
  Google Scholar
• 59. Sass P., Bierbaum G.: Lytic activity of recombinant bacteriophageφ11 and φ12 endolysins on whole cells and biofilms of Staphylococcusaureus. Appl. Environ. Microbiol., 2007; 73: 347-352
  Google Scholar
• 60. Savva C.G., Dewey J.S., Deaton J., White R.L., Struck D.K., HolzenburgA., Young R.: The holin of bacteriophage lambda forms ringswith large diameter. Mol. Microbiol., 2008; 69: 784-793
  Google Scholar
• 61. Savva C.G., Dewey J.S., Moussa S.H., To K.H., Holzenburg A.,Young R.: Stable micron-scale holes are a general feature of canonicalholins. Mol. Microbiol., 2014; 91: 57-65
  Google Scholar
• 62. Schleifer K.H., Kandler O.: Peptidoglycan types of bacterial cellwalls and their taxonomic implications. Bacteriol. Rev., 1972; 36:407-477
  Google Scholar
• 63. Schmidt C., Velleman M., Arber W.: Three functions of bacteriophageP1 involved in cell lysis. J. Bacteriol., 1996; 178: 1099-1104
  Google Scholar
• 64. Silhavy T.J., Kahne D., Walker S.: The bacterial cell envelope.Cold Spring Harb. Perspect. Biol., 2010; 2: a000414
  Google Scholar
• 65. Smith D.L., Struck D.K., Scholtz J.M., Young R.: Purification andbiochemical characterization of the lambda holin. J. Bacteriol., 1998;180: 2531-2540
  Google Scholar
• 66. Sun Q., Kuty G.F., Arockiasamy A., Xu M., Young R., SacchettiniJ.C.: Regulation of a muralytic enzyme by dynamic membrane topology.Nat. Struct. Mol. Biol., 2009; 16: 1192-1194
  Google Scholar
• 67. Wang I.N., Deaton J., Young R.: Sizing the holin lesion with anendolysin-β-galactosidase fusion. J. Bacteriol., 2003; 185: 779-787
  Google Scholar
• 68. Wang I.N., Dykhuizen D.E., Slobodkin L.B.: The evolution of phagelysis timing. Evol. Ecol., 1996; 10: 545-558
  Google Scholar
• 69. Wang I.N., Smith D.L., Young R.: Holins: the protein clocks ofbacteriophage infections. Annu. Rev. Microbiol., 2000; 54: 799-825
  Google Scholar
• 70. White R., Chiba S., Pang T., Dewey J.S., Savva C.G., HolzenburgA., Pogliano K., Young R.: Holin triggering in real time. Proc. Natl.Acad. Sci. USA, 2011; 108: 798-803
  Google Scholar
• 71. Xu M., Arulandu A., Struck D.K., Swanson S., Sacchettini J.C.,Young R.: Disulfide isomerization after membrane release of its SARdomain activates P1 lysozyme. Science, 2005; 307: 113-117
  Google Scholar
• 72. Xu M., Struck D.K., Deaton J., Wang I.N., Young R.: A signal-arrest-releasesequence mediates export and control of the phage P1endolysin. Proc. Natl. Acad. Sci. USA, 2004; 101: 6415-6420
  Google Scholar
• 73. Young R.: Bacteriophage holins: deadly diversity. J. Mol. Microbiol.Biotechnol., 2002; 4: 21-36
  Google Scholar
• 74. Young R.: Phage lysis. W: Phages. Their Role in Bacterial Pathogenesisand Biotechnology, red.: Waldor K.M., Friedman D.I., AdhyaS.A., ASM Press, Washington D.C., 2005; 92-128
  Google Scholar
• 75. Young R.: Phage lysis: three steps, three choices, one outcome.J. Microbiol., 2014; 52: 243-258
  Google Scholar
• 76. Young R., Wang I.N.: Phage lysis, W: The Bacteriophages, red.:R. Calendar and S.T. Abedon, Oxford University Press, Oxford, 2006;104-126
  Google Scholar
• 77. Young R., Wang I.N., Roof W.D.: Phages will out: strategies ofhost cell lysis. Trends Microbiol., 2000; 8: 120-128
  Google Scholar
• 78. Zheng Y., Struck D.K., Young R.: Purification and functionalcharacterization of ϕX174 lysis protein E. Biochemistry, 2009; 48:4999-5006
  Google Scholar

Full text