title: Commitment to lysogeny is preceded by a prolonged period of sensitivity to the late lytic regulator Q in bacteriophage λ.
abstract: A key event in development is the irreversible commitment to a particular cell fate, which may be concurrent with or delayed with respect to the initial cell fate decision. In this work, we use the paradigmatic bacteriophage λ lysis-lysogeny decision circuit to study the timing of commitment. The lysis-lysogeny decision is made based on the expression trajectory of CII. The chosen developmental strategy is manifested by repression of the pR and pL promoters by CI (lysogeny) or by antitermination of late gene expression by Q (lysis). We found that expression of Q in trans from a plasmid at the time of infection resulted in a uniform lytic decision. Furthermore, expression of Q up to 50 min after infection results in lysis of the majority of cells which initially chose lysogenic development. In contrast, expression of Q in cells containing a single chromosomal prophage had no effect on cell growth, indicating commitment to lysogeny. Notably, if the prophage was present in 10 plasmid-borne copies, Q expression resulted in lytic development, suggesting that the cellular phage chromosome number is the critical determinant of the timing of lysogenic commitment. Based on our results, we conclude that (i) the lysogenic decision made by the CI-Cro switch soon after infection can be overruled by ectopic Q expression at least for a time equivalent to one phage life cycle, (ii) the presence of multiple λ chromosomes is a prerequisite for a successful Q-mediated switch from lysogenic to lytic development, and (iii) phage chromosomes within the same cell can reach different decisions.
authors.affiliation: Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sine Lo
authors.initials: SL
authors.lastname: Svenningsen
authors.affiliation: Center for Models of Life, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark semsey@nbi.dk.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Semsey
mesh_terms: D010582:Bacteriophage lambda; D004926:Escherichia coli / Q000166:cytology / Q000821:virology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D008242:Lysogeny; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C066119:Q protein, Bacteriophage lambda; D014764:Viral Proteins
references.citation: PLoS One. 2008 Jun 11;3(6):e2351
references.pmid: 18545653
references.citation: Genes Dev. 1987 May;1(3):217-26
references.pmid: 2960589
references.citation: Cell. 2010 May 14;141(4):682-91
references.pmid: 20478257
references.citation: PLoS Comput Biol. 2011 Nov;7(11):e1002273
references.pmid: 22102806
references.citation: J Bacteriol. 1998 Mar;180(6):1573-7
references.pmid: 9515930
references.citation: Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4470-5
references.pmid: 15728384
references.citation: Nature. 2010 May 6;465(7294):101-5
references.pmid: 20400943
references.citation: J Virol. 1979 Apr;30(1):14-20
references.pmid: 158098
references.citation: J Bacteriol. 1953 Jun;65(6):642-51
references.pmid: 13069436
references.citation: Mol Cell. 2009 Jun 12;34(5):545-55
references.pmid: 19524535
references.citation: Annu Rev Genet. 2005;39:409-29
references.pmid: 16285866
references.citation: Science. 1998 May 8;280(5365):895-8
references.pmid: 9572732
references.citation: Stem Cells Dev. 2005 Apr;14(2):111-21
references.pmid: 15910238
references.citation: Biochim Biophys Acta. 1975 Sep 12;407(1):83-90
references.pmid: 1101966
references.citation: Epigenetics. 2009 Feb 16;4(2):89-92
references.pmid: 19287212
references.citation: Gene. 1982 Jun;18(3):335-41
references.pmid: 6290337
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8168-72
references.pmid: 9223333
references.citation: J Mol Biol. 1970 Feb 14;47(3):545-56
references.pmid: 5418171
references.citation: Cold Spring Harb Symp Quant Biol. 1953;18:71-3
references.pmid: 13168971
references.citation: Microbiology (Reading). 2012 Feb;158(Pt 2):488-497
references.pmid: 22096150
references.citation: Proc Natl Acad Sci U S A. 1985 May;82(10):3134-8
references.pmid: 3159014
references.citation: J Mol Biol. 1974 May 5;85(1):163-75
references.pmid: 4835731
references.citation: Virology. 1983 Apr 15;126(1):168-82
references.pmid: 6221468
references.citation: J Bacteriol. 1995 Jul;177(14):4121-30
references.pmid: 7608087
references.citation: J Bacteriol. 1974 Sep;119(3):736-47
references.pmid: 4604283
references.citation: J Mol Biol. 2003 Nov 28;334(3):363-72
references.pmid: 14623180