1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

Mechanisms of Theta Plasmid Replication

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • XML
    92.19 Kb
  • PDF
    317.53 Kb
  • HTML
    102.02 Kb
  • Authors: Joshua Lilly1, Manel Camps2
  • Editors: Marcelo Tolmasky3, Juan Carlos Alonso4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064; 2: Department of Microbiology and Environmental Toxicology, University of California Santa Cruz, Santa Cruz, CA 95064; 3: California State University, Fullerton, CA; 4: Centro Nacional de Biotecnología, Cantoblanco, Madrid, Spain
  • Source: microbiolspec January 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.PLAS-0029-2014
  • Received 11 November 2014 Accepted 11 November 2014 Published 16 January 2015
  • Manel Camps, mcamps@ucsc.edu
image of Mechanisms of Theta Plasmid Replication
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Mechanisms of Theta Plasmid Replication, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/3/1/PLAS-0029-2014-1.gif /docserver/preview/fulltext/microbiolspec/3/1/PLAS-0029-2014-2.gif
  • Abstract:

    Plasmids are autonomously replicating pieces of DNA. This article discusses theta plasmid replication, which is a class of circular plasmid replication that includes ColE1-like origins of replication popular with expression vectors. All modalities of theta plasmid replication initiate synthesis with the leading strand at a predetermined site and complete replication through recruitment of the host's replisome, which extends the leading strand continuously while synthesizing the lagging strand discontinuously. There are clear differences between different modalities of theta plasmid replication in mechanisms of DNA duplex melting and in priming of leading- and lagging-strand synthesis. In some replicons duplex melting depends on transcription, while other replicons rely on plasmid-encoded -acting proteins (Reps); primers for leading-strand synthesis can be generated through processing of a transcript or in other replicons by the action of host- or plasmid-encoded primases. None of these processes require DNA breaks. The frequency of replication initiation is tightly regulated to facilitate establishment in permissive hosts and to achieve a steady state. The last section of the article reviews how plasmid copy number is sensed and how this feedback modulates the frequency of replication.

  • Citation: Lilly J, Camps M. 2015. Mechanisms of Theta Plasmid Replication. Microbiol Spectrum 3(1):PLAS-0029-2014. doi:10.1128/microbiolspec.PLAS-0029-2014.

Key Concept Ranking

DNA Synthesis
0.47614172
0.47614172

References

1. Giraldo R, Fernandez-Tresguerres ME. 2004. Twenty years of the pPS10 replicon: insights on the molecular mechanism for the activation of DNA replication in iteron-containing bacterial plasmids. Plasmid 52:69–83.[PubMed][CrossRef]
2. Kittleson JT, Cheung S, Anderson JC. 2011. Rapid optimization of gene dosage in E. coli using DIAL strains. J Biol Eng 5:10. [PubMed][CrossRef]
3. Gregg AV, McGlynn P, Jaktaji RP, Lloyd RG. 2002. Direct rescue of stalled DNA replication forks via the combined action of PriA and RecG helicase activities. Mol Cell 9:241–251. [PubMed][CrossRef]
4. Kogoma T. 1997. Stable DNA replication: interplay between DNA replication, homologous recombination, and transcription. Microbiol Mol Biol Rev 61:212–238. [PubMed]
5. Sandler SJ, Marians KJ. 2000. Role of PriA in replication fork reactivation in Escherichia coli. J Bacteriol 182:9–13. [PubMed][CrossRef]
6. Masai H, Arai K. 1996. DnaA- and PriA-dependent primosomes: two distinct replication complexes for replication of Escherichia coli chromosome. Front Biosci 1:d48–d58. [PubMed]
7. Wu CA, Zechner EL, Marians KJ. 1992. Coordinated leading- and lagging-strand synthesis at the Escherichia coli DNA replication fork. I. Multiple effectors act to modulate Okazaki fragment size. J Biol Chem 267:4030–4044. [PubMed]
8. Johnson A, O'Donnell M. 2005. Cellular DNA replicases: components and dynamics at the replication fork. Annu Rev Biochem 74:283–315. [PubMed][CrossRef]
9. McHenry CS. 2011. DNA replicases from a bacterial perspective. Annu Rev Biochem 80:403–436. [PubMed][CrossRef]
10. Tanner NA, Hamdan SM, Jergic S, Loscha KV, Schaeffer PM, Dixon NE, van Oijen AM. 2008. Single-molecule studies of fork dynamics in Escherichia coli DNA replication. Nat Struct Mol Biol 15:998. [PubMed][CrossRef]
11. Lenhart JS, Schroeder JW, Walsh BW, Simmons LA. 2012. DNA repair and genome maintenance in Bacillus subtilis. Microbiol Mol Biol Rev 76:530–564. [PubMed][CrossRef]
12. Rannou O, Le Chatelier E, Larson MA, Nouri H, Dalmais B, Laughton C, Janniere L, Soultanas P. 2013. Functional interplay of DnaE polymerase, DnaG primase and DnaC helicase within a ternary complex, and primase to polymerase hand-off during lagging strand DNA replication in Bacillus subtilis. Nucleic Acids Res 41:5303–5320. [PubMed][CrossRef]
13. Allen JM, Simcha DM, Ericson NG, Alexander DL, Marquette JT, Van Biber BP, Troll CJ, Karchin R, Bielas JH, Loeb LA, Camps M. 2011. Roles of DNA polymerase I in leading and lagging-strand replication defined by a high-resolution mutation footprint of ColE1 plasmid replication. Nucleic Acids Res 39:7020–7033. [PubMed][CrossRef]
14. Patel PH, Suzuki M, Adman E, Shinkai A, Loeb LA. 2001. Prokaryotic DNA polymerase I: evolution, structure, and “base flipping” mechanism for nucleotide selection. J Mol Biol 308:823–837. [PubMed][CrossRef]
15. Maki H, Bryan SK, Horiuchi T, Moses RE. 1989. Suppression of dnaE nonsense mutations by pcbA1. J Bacteriol 171:3139–3143. [PubMed]
16. Troll C, Yoder J, Alexander D, Hernandez J, Loh Y, Camps M. 2014. The mutagenic footprint of low-fidelity Pol I ColE1 plasmid replication in E. coli reveals an extensive interplay between Pol I and Pol III. Curr Genet 60:123–134. [PubMed][CrossRef]
17. Mukhopadhyay G, Chattoraj DK. 1993. Conformation of the origin of P1 plasmid replication. Initiator protein induced wrapping and intrinsic unstacking. J Mol Biol 231:19–28. [PubMed][CrossRef]
18. Urh M, Wu J, Wu J, Forest K, Inman RB, Filutowicz M. 1998. Assemblies of replication initiator protein on symmetric and asymmetric DNA sequences depend on multiple protein oligomerization surfaces. J Mol Biol 283:619–631. [PubMed][CrossRef]
19. Filutowicz M, Dellis S, Levchenko I, Urh M, Wu F, York D. 1994. Regulation of replication of an iteron-containing DNA molecule. Prog Nucleic Acid Res Mol Biol 48:239–273. [PubMed][CrossRef]
20. Stenzel TT, MacAllister T, Bastia D. 1991. Cooperativity at a distance promoted by the combined action of two replication initiator proteins and a DNA bending protein at the replication origin of pSC101. Genes Dev 5:1453–1463. [PubMed][CrossRef]
21. Park K, Chattoraj DK. 2001. DnaA boxes in the P1 plasmid origin: the effect of their position on the directionality of replication and plasmid copy number. J Mol Biol 310:69–81. [PubMed][CrossRef]
22. Doran KS, Helinski DR, Konieczny I. 1999. Host-dependent requirement for specific DnaA boxes for plasmid RK2 replication. Mol Microbiol 33:490–498. [PubMed][CrossRef]
23. del Solar G, Giraldo R, Ruiz-Echevarria MJ, Espinosa M, and Diaz-Orejas R. 1998. Replication and control of circular bacterial plasmids. Microbiol Mol Biol Rev 62:434–464. [PubMed]
24. Rakowski SA, Filutowicz M. 2013. Plasmid R6K replication control. Plasmid 69:231–242. [PubMed][CrossRef]
25. Wu YC, Liu ST. 2010. A sequence that affects the copy number and stability of pSW200 and ColE1. J Bacteriol 192:3654–3660. [PubMed][CrossRef]
26. Masukata H, Tomizawa J. 1986. Control of primer formation for ColE1 plasmid replication: conformational change of the primer transcript. Cell 44:125–136. [PubMed][CrossRef]
27. Camps M. 2010. Modulation of ColE1-like plasmid replication for recombinant gene expression. Recent Pat DNA Gene Seq 4:58–73. [PubMed][CrossRef]
28. Cesareni G, Helmer-Citterich M, Castagnoli L. 1991. Control of ColE1 plasmid replication by antisense RNA. Trends Genet 7:230–235. [PubMed][CrossRef]
29. Wang Z, Yuan Z, Hengge UR. 2004. Processing of plasmid DNA with ColE1-like replication origin. Plasmid 51:149–161. [PubMed][CrossRef]
30. Lee EH, Kornberg A. 1991. Replication deficiencies in priA mutants of Escherichia coli lacking the primosomal replication n' protein. Proc Natl Acad Sci USA 88:3029–3032. [CrossRef]
31. Sandler SJ, Samra HS, Clark AJ. 1996. Differential suppression of priA2::kan phenotypes in Escherichia coli K-12 by mutations in priA, lexA, and dnaC. Genetics 143:5–13. [PubMed]
32. Jaktaji RP, Lloyd RG. 2003. PriA supports two distinct pathways for replication restart in UV-irradiated Escherichia coli cells. Mol Microbiol 47:1091–1100. [PubMed][CrossRef]
33. Nakasu S, Tomizawa J. 1992. Structure of the ColE1 DNA molecule before segregation to daughter molecules. Proc Natl Acad Sci USA 89:10139–10143. [PubMed][CrossRef]
34. Drolet M. 2006. Growth inhibition mediated by excess negative supercoiling: the interplay between transcription elongation, R-loop formation and DNA topology. Mol Microbiol 59:723–730. [PubMed][CrossRef]
35. Drolet M, Broccoli S, Rallu F, Hraiky C, Fortin C, Masse E, Baaklini I. 2003. The problem of hypernegative supercoiling and R-loop formation in transcription. Front Biosci 8:d210-d221. [PubMed][CrossRef]
36. Gowrishankar J, Harinarayanan R. 2004. Why is transcription coupled to translation in bacteria? Mol Microbiol 54:598–603. [PubMed][CrossRef]
37. Fukuoh A, Iwasaki H, Ishioka K, Shinagawa H. 1997. ATP-dependent resolution of R-loops at the ColE1 replication origin by Escherichia coli RecG protein, a Holliday junction-specific helicase. EMBO J 16:203–209. [PubMed][CrossRef]
38. del Solar G, Alonso JC, Espinosa M, Diaz-Orejas R. 1996. Broad-host-range plasmid replication: an open question. Mol Microbiol 21:661–666. [PubMed][CrossRef]
39. Yasueda H, Horii T, Itoh T. 1989. Structural and functional organization of ColE2 and ColE3 replicons. Mol Gen Genet 215:209–216. [PubMed][CrossRef]
40. Aoki K, Shinohara M, Itoh T. 2007. Distinct functions of the two specificity determinants in replication initiation of plasmids ColE2-P9 and ColE3-CA38. J Bacteriol 189:2392–2400. [PubMed][CrossRef]
41. Takechi S, Matsui H, Itoh T. 1995. Primer RNA synthesis by plasmid-specified Rep protein for initiation of ColE2 DNA replication. EMBO J 14:5141–5147. [PubMed]
42. Takechi S, Itoh T. 1995. Initiation of unidirectional ColE2 DNA replication by a unique priming mechanism. Nucleic Acids Res 23:4196–4201. [PubMed][CrossRef]
43. Bruand C, Ehrlich SD. 1998. Transcription-driven DNA replication of plasmid pAMbeta1 in Bacillus subtilis. Mol Microbiol 30:135–145. [PubMed][CrossRef]
44. Le Chatelier E, Janniere L, Ehrlich SD, Canceill D. 2001. The RepE initiator is a double-stranded and single-stranded DNA-binding protein that forms an atypical open complex at the onset of replication of plasmid pAMbeta 1 from Gram-positive bacteria. J Biol Chem 276:10234–10246. [PubMed][CrossRef]
45. Brantl S. 2014. Antisense-RNA mediated control of plasmid replication: pIP501 revisited. Plasmid. [Epub ahead of print.] doi:10.1016/j.plasmid.2014.07.004. [CrossRef]
46. Bidnenko V, Ehrlich SD, Janniere L. 1998. In vivo relations between pAMbeta1-encoded type I topoisomerase and plasmid replication. Mol Microbiol 28:1005–1016. [PubMed][CrossRef]
47. Janniere L, Bidnenko V, McGovern S, Ehrlich SD, Petit MA. 1997. Replication terminus for DNA polymerase I during initiation of pAM beta 1 replication: role of the plasmid-encoded resolution system. Mol Microbiol 23:525–535. [PubMed][CrossRef]
48. Sakai H, Komano T. 1996. DNA replication of IncQ broad-host-range plasmids in Gram-negative bacteria. Biosci Biotechnol Biochem 60:377–382. [PubMed][CrossRef]
49. Loftie-Eaton W, Rawlings DE. 2012. Diversity, biology and evolution of IncQ-family plasmids. Plasmid 67:15–34. [PubMed][CrossRef]
50. Honda Y, Akioka T, Takebe S, Tanaka K, Miao D, Higashi A, Nakamura T, Taguchi Y, Sakai H, Komano T. 1993. Mutational analysis of the specific priming signal essential for DNA replication of the broad host-range plasmid RSF1010. FEBS Lett 324:67–70. [PubMed][CrossRef]
51. Miao DM, Honda Y, Tanaka K, Higashi A, Nakamura T, Taguchi Y, Sakai H, Komano T, Bagdasarian M. 1993. A base-paired hairpin structure essential for the functional priming signal for DNA replication of the broad host range plasmid RSF1010. Nucleic Acids Res 21:4900–4903. [PubMed][CrossRef]
52. Rawlings DE, Tietze E. 2001. Comparative biology of IncQ and IncQ-like plasmids. Microbiol Mol Biol Rev 65:481–496. [PubMed][CrossRef]
53. Tanaka K, Kino K, Taguchi Y, Miao DM, Honda Y, Sakai H, Komano T, Bagdasarian M. 1994. Functional difference between the two oppositely oriented priming signals essential for the initiation of the broad host-range plasmid RSF1010 DNA replication. Nucleic Acids Res 22:767–772. [PubMed][CrossRef]
54. Nordstrom K, Wagner EG. 1994. Kinetic aspects of control of plasmid replication by antisense RNA. Trends Biochem Sci 19:294–300. [PubMed][CrossRef]
55. del Solar G, Espinosa M. 2000. Plasmid copy number control: an ever-growing story. Mol Microbiol 37:492–500. [PubMed][CrossRef]
56. Wagner EG, Altuvia S, Romby P. 2002. Antisense RNAs in bacteria and their genetic elements. Adv Genet 46:361–398. [PubMed][CrossRef]
57. Brantl S. 2014. Plasmid replication control by antisense RNAs. In Tolmasky ME, Alonso JC (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. In press.
58. Hjalt TA, Wagner EG. 1995. Bulged-out nucleotides in an antisense RNA are required for rapid target RNA binding in vitro and inhibition in vivo. Nucleic Acids Res 23:580–587. [PubMed][CrossRef]
59. Go H, Lee K. 2011. A genetic system for RNase E variant-controlled overproduction of ColE1-type plasmid DNA. J Biotechnol 152:171–175. [PubMed][CrossRef]
60. Nishio SY, Itoh T. 2008. Replication initiator protein mRNA of ColE2 plasmid and its antisense regulator RNA are under the control of different degradation pathways. Plasmid 59:102–110. [PubMed][CrossRef]
61. Xu FF, Gaggero C, Cohen SN. 2002. Polyadenylation can regulate ColE1 type plasmid copy number independently of any effect on RNAI decay by decreasing the interaction of antisense RNAI with its RNAII target. Plasmid 48:49–58. [PubMed][CrossRef]
62. Nishio SY, Itoh T. 2008. The effects of RNA degradation enzymes on antisense RNAI controlling ColE2 plasmid copy number. Plasmid 60:174–180. [PubMed][CrossRef]
63. Binnie U, Wong K, McAteer S, Masters M. 1999. Absence of RNASE III alters the pathway by which RNAI, the antisense inhibitor of ColE1 replication, decays. Microbiology 145(Pt 11):3089–3100. [PubMed]
64. Nishio SY, Itoh T. 2009. Arginine-rich RNA binding domain and protein scaffold domain of RNase E are important for degradation of RNAI but not for that of the Rep mRNA of the ColE2 plasmid. Plasmid 62:83–87. [PubMed][CrossRef]
65. Polisky B. 1988. ColE1 replication control circuitry: sense from antisense. Cell 55:929–932. [PubMed][CrossRef]
66. Yavachev L, Ivanov I. 1988. What does the homology between E. coli tRNAs and RNAs controlling ColE1 plasmid replication mean? J Theor Biol 131:235–241. [CrossRef]
67. Wang Z, Yuan Z, Xiang L, Shao J, Wegrzyn G. 2006. tRNA-dependent cleavage of the ColE1 plasmid-encoded RNA I. Microbiology 152:3467–3476. [PubMed][CrossRef]
68. Wang Z, Le G, Shi Y, Wegrzyn G, Wrobel B. 2002. A model for regulation of ColE1-like plasmid replication by uncharged tRNAs in amino acid-starved Escherichia coli cells. Plasmid 47:69–78. [PubMed][CrossRef]
69. Grabherr R, Nilsson E, Striedner G, Bayer K. 2002. Stabilizing plasmid copy number to improve recombinant protein production. Biotechnol Bioeng 77:142–147. [PubMed][CrossRef]
70. Hiraga S, Sugiyama T, Itoh T. 1994. Comparative analysis of the replicon regions of eleven ColE2-related plasmids. J Bacteriol 176:7233–7243. [PubMed]
71. Malmgren C, Engdahl HM, Romby P, Wagner EG. 1996. An antisense/target RNA duplex or a strong intramolecular RNA structure 5′ of a translation initiation signal blocks ribosome binding: the case of plasmid R1. RNA 2:1022–1032. [PubMed]
72. Brantl S, Birch-Hirschfeld E, Behnke D. 1993. RepR protein expression on plasmid pIP501 is controlled by an antisense RNA-mediated transcription attenuation mechanism. J Bacteriol 175:4052–4061. [PubMed]
73. Giraldo R, Fernandez-Tornero C, Evans PR, Diaz-Orejas R, Romero A. 2003. A conformational switch between transcriptional repression and replication initiation in the RepA dimerization domain. Nat Struct Biol 10:565–571. [PubMed][CrossRef]
74. DasGupta S, Mukhopadhyay G, Papp PP, Lewis MS, Chattoraj DK. 1993. Activation of DNA binding by the monomeric form of the P1 replication initiator RepA by heat shock proteins DnaJ and DnaK. J Mol Biol 232:23–34. [PubMed][CrossRef]
75. Diaz-Lopez T, Lages-Gonzalo M, Serrano-Lopez A, Alfonso C, Rivas G, Diaz-Orejas R, Giraldo R. 2003. Structural changes in RepA, a plasmid replication initiator, upon binding to origin DNA. J Biol Chem 278:18606–18616. [PubMed][CrossRef]
76. Kawasaki Y, Wada C, Yura T. 1990. Roles of Escherichia coli heat shock proteins DnaK, DnaJ and GrpE in mini-F plasmid replication. Mol Gen Genet 220:277–282. [PubMed][CrossRef]
77. Wickner S, Skowyra D, Hoskins J, McKenney K. 1992. DnaJ, DnaK, and GrpE heat shock proteins are required in oriP1 DNA replication solely at the RepA monomerization step. Proc Natl Acad Sci USA 89:10345–10349. [PubMed][CrossRef]
78. Gasset-Rosa F, Diaz-Lopez T, Lurz R, Prieto A, Fernandez-Tresguerres ME, Giraldo R. 2008. Negative regulation of pPS10 plasmid replication: origin pairing by zipping-up DNA-bound RepA monomers. Mol Microbiol 68:560–572. [PubMed][CrossRef]
79. Park K, Han E, Paulsson J, Chattoraj DK. 2001. Origin pairing (‘handcuffing’) as a mode of negative control of P1 plasmid copy number. EMBO J 20:7323–7332. [PubMed][CrossRef]
80. Zzaman S, Bastia D. 2005. Oligomeric initiator protein-mediated DNA looping negatively regulates plasmid replication in vitro by preventing origin melting. Mol Cell 20:833–843. [PubMed][CrossRef]
81. Das N, Valjavec-Gratian M, Basuray AN, Fekete RA, Papp PP, Paulsson J, Chattoraj DK. 2005. Multiple homeostatic mechanisms in the control of P1 plasmid replication. Proc Natl Acad Sci USA 102:2856–2861. [PubMed][CrossRef]
microbiolspec.PLAS-0029-2014.citations
cm/3/1
content/journal/microbiolspec/10.1128/microbiolspec.PLAS-0029-2014
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.PLAS-0029-2014
2015-01-16
2017-08-18

Abstract:

Plasmids are autonomously replicating pieces of DNA. This article discusses theta plasmid replication, which is a class of circular plasmid replication that includes ColE1-like origins of replication popular with expression vectors. All modalities of theta plasmid replication initiate synthesis with the leading strand at a predetermined site and complete replication through recruitment of the host's replisome, which extends the leading strand continuously while synthesizing the lagging strand discontinuously. There are clear differences between different modalities of theta plasmid replication in mechanisms of DNA duplex melting and in priming of leading- and lagging-strand synthesis. In some replicons duplex melting depends on transcription, while other replicons rely on plasmid-encoded -acting proteins (Reps); primers for leading-strand synthesis can be generated through processing of a transcript or in other replicons by the action of host- or plasmid-encoded primases. None of these processes require DNA breaks. The frequency of replication initiation is tightly regulated to facilitate establishment in permissive hosts and to achieve a steady state. The last section of the article reviews how plasmid copy number is sensed and how this feedback modulates the frequency of replication.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

/deliver/fulltext/microbiolspec/3/1/PLAS-0029-2014.html?itemId=/content/journal/microbiolspec/10.1128/microbiolspec.PLAS-0029-2014&mimeType=html&fmt=ahah

Figures

Image of FIGURE 1

Click to view

FIGURE 1

Model of plasmid replication by the strand-displacement mechanism. (I) Parental DNA duplex (solid black lines) depicting the two single-stranded replication initiation sites, (light gray box) and (dark gray box). Vertical lines show hybridization between DNA strands. (II) The DNA duplex is melted through binding of RepC (possibly in concert with the RepA helicase), allowing the two sites to form hairpins (ball and stick). (III) The base of the hairpin is recognized by RepB′, which initiates the synthesis of an RNA primer (light gray dashed line). Extension of the free 3′-OH of the primer by Pol III (assisted by the RepA helicase) is shown as dashed black arrows. Two D-loops are formed, one for each direction of synthesis, as parental strands are displaced and dissociate from each other, leaving ssDNA intermediates. This is shown as areas where one of the strands has no hydrogen bonding. (IV) Synthesis continues in both directions, extending the area of D-loop formation. (V) Elongation is completed and termination of replication occurs on both strands at the sites in which replication began. At this point, the sites on the newly synthesized daughter strands are restored. (VI) Segregation: the two daughter strands are ligated, resulting in two DNA duplexes, each containing a parental strand (solid black line) and daughter strand (dashed black line). doi:10.1128/microbiolspec.PLAS-0029-2014.f1

Source: microbiolspec January 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.PLAS-0029-2014
Permissions and Reprints Request Permissions
Download as Powerpoint

Tables

Generic image for table

Click to view

TABLE 1

Comparison of the three basic modes of plasmid replication initiation in circular plasmids

Source: microbiolspec January 2015 vol. 3 no. 1 doi:10.1128/microbiolspec.PLAS-0029-2014

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error