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Natural and Artificial Strategies To Control the Conjugative Transmission of Plasmids

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  • Authors: María Getino1,2, Fernando de la Cruz3
  • Editors: Fernando Baquero4, Emilio Bouza5, J.A. Gutiérrez-Fuentes6, Teresa M. Coque7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: School of Biosciences and Medicine, University of Surrey, Guildford, United Kingdom; 2: Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria–Consejo Superior de Investigaciones Científicas, Santander, Spain.; 3: Instituto de Biomedicina y Biotecnología de Cantabria, Universidad de Cantabria–Consejo Superior de Investigaciones Científicas, Santander, Spain.; 4: Hospital Ramón y Cajal (IRYCIS), Madrid, Spain; 5: Hospital Ramón y Cajal (IRYCIS), Madrid, Spain; 6: Complutensis University, Madrid, Spain; 7: Hospital Ramón y Cajal (IRYCIS), Madrid, Spain
    • Source: microbiolspec January 2018 vol. 6 no. 1 doi:10.1128/microbiolspec.MTBP-0015-2016
  • Received 17 February 2017 Accepted 26 June 2017 Published 11 January 2018
  • Fernando de la Cruz, [email protected]
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  • Abstract:

    Conjugative plasmids are the main carriers of transmissible antibiotic resistance (AbR) genes. For that reason, strategies to control plasmid transmission have been proposed as potential solutions to prevent AbR dissemination. Natural mechanisms that bacteria employ as defense barriers against invading genomes, such as restriction-modification or CRISPR-Cas systems, could be exploited to control conjugation. Besides, conjugative plasmids themselves display mechanisms to minimize their associated burden or to compete with related or unrelated plasmids. Thus, FinOP systems, composed of FinO repressor protein and FinP antisense RNA, aid plasmids to regulate their own transfer; exclusion systems avoid conjugative transfer of related plasmids to the same recipient bacteria; and fertility inhibition systems block transmission of unrelated plasmids from the same donor cell. Artificial strategies have also been designed to control bacterial conjugation. For instance, intrabodies against R388 relaxase expressed in recipient cells inhibit plasmid R388 conjugative transfer; pIII protein of bacteriophage M13 inhibits plasmid F transmission by obstructing conjugative pili; and unsaturated fatty acids prevent transfer of clinically relevant plasmids in different hosts, promoting plasmid extinction in bacterial populations. Overall, a number of exogenous and endogenous factors have an effect on the sophisticated process of bacterial conjugation. This review puts them together in an effort to offer a wide picture and inform research to control plasmid transmission, focusing on Gram-negative bacteria.

  • Citation: Getino M, de la Cruz F. 2018. Natural and Artificial Strategies To Control the Conjugative Transmission of Plasmids. Microbiol Spectrum 6(1):MTBP-0015-2016. doi:10.1128/microbiolspec.MTBP-0015-2016.

References

1. Fleming A. 1929. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. Influenzae. Br J Exp Pathol 10:226–236. [PubMed]
2. D’Costa VM, McGrann KM, Hughes DW, Wright GD. 2006. Sampling the antibiotic resistome. Science 311:374–377. http://dx.doi.org/10.1126/science.1120800.
3. Davies J, Davies D. 2010. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 74:417–433. http://dx.doi.org/10.1128/MMBR.00016-10. [PubMed]
4. Clatworthy AE, Pierson E, Hung DT. 2007. Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol 3:541–548. http://dx.doi.org/10.1038/nchembio.2007.24. [PubMed]
5. Liu B, Pop M. 2009. ARDB—Antibiotic Resistance Genes Database. Nucleic Acids Res 37(Database issue) :D443–D447. http://dx.doi.org/10.1093/nar/gkn656. [PubMed]
6. Cooper MA, Shlaes D. 2011. Fix the antibiotics pipeline. Nature 472:32. http://dx.doi.org/10.1038/472032a. [PubMed]
7. O’Neill J. 2014. Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. Review on Antimicrobial Resistance, London, United Kingdom. https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf.
8. Heras B, Scanlon MJ, Martin JL. 2015. Targeting virulence not viability in the search for future antibacterials. Br J Clin Pharmacol 79:208–215. http://dx.doi.org/10.1111/bcp.12356. [PubMed]
9. Scully IL, Swanson K, Green L, Jansen KU, Anderson AS. 2015. Anti-infective vaccination in the 21st century—new horizons for personal and public health. Curr Opin Microbiol 27:96–102. http://dx.doi.org/10.1016/j.mib.2015.07.006. [PubMed]
10. Nobrega FL, Costa AR, Kluskens LD, Azeredo J. 2015. Revisiting phage therapy: new applications for old resources. Trends Microbiol 23:185–191. http://dx.doi.org/10.1016/j.tim.2015.01.006. [PubMed]
11. Dwidar M, Monnappa AK, Mitchell RJ. 2012. The dual probiotic and antibiotic nature of Bdellovibrio bacteriovorus. BMB Rep 45:71–78. http://dx.doi.org/10.5483/BMBRep.2012.45.2.71. [PubMed]
12. Williams JJ, Hergenrother PJ. 2008. Exposing plasmids as the Achilles’ heel of drug-resistant bacteria. Curr Opin Chem Biol 12:389–399. http://dx.doi.org/10.1016/j.cbpa.2008.06.015. [PubMed]
13. Thomas CM, Nielsen KM. 2005. Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nat Rev Microbiol 3:711–721. http://dx.doi.org/10.1038/nrmicro1234. [PubMed]
14. Baquero F, Coque TM, de la Cruz F. 2011. Ecology and evolution as targets: the need for novel eco-evo drugs and strategies to fight antibiotic resistance. Antimicrob Agents Chemother 55:3649–3660. http://dx.doi.org/10.1128/AAC.00013-11. [PubMed]
15. Lawrence JG, Retchless AC. 2009. The interplay of homologous recombination and horizontal gene transfer in bacterial speciation. Methods Mol Biol 532:29–53. http://dx.doi.org/10.1007/978-1-60327-853-9_3. [PubMed]
16. Frost LS, Leplae R, Summers AO, Toussaint A. 2005. Mobile genetic elements: the agents of open source evolution. Nat Rev Microbiol 3:722–732. http://dx.doi.org/10.1038/nrmicro1235. [PubMed]
17. Davison J. 1999. Genetic exchange between bacteria in the environment. Plasmid 42:73–91. http://dx.doi.org/10.1006/plas.1999.1421. [PubMed]
18. Halary S, Leigh JW, Cheaib B, Lopez P, Bapteste E. 2010. Network analyses structure genetic diversity in independent genetic worlds. Proc Natl Acad Sci U S A 107:127–132. http://dx.doi.org/10.1073/pnas.0908978107. [PubMed]
19. Amábile-Cuevas CF, Chicurel ME. 1992. Bacterial plasmids and gene flux. Cell 70:189–199. http://dx.doi.org/10.1016/0092-8674(92)90095-T. [PubMed]
20. Smillie C, Garcillán-Barcia MP, Francia MV, Rocha EP, de la Cruz F. 2010. Mobility of plasmids. Microbiol Mol Biol Rev 74:434–452. http://dx.doi.org/10.1128/MMBR.00020-10. [PubMed]
21. Waters VL. 1999. Conjugative transfer in the dissemination of beta-lactam and aminoglycoside resistance. Front Biosci 4:D433–D456. http://dx.doi.org/10.2741/A439. [PubMed]
22. Norman A, Hansen LH, Sørensen SJ. 2009. Conjugative plasmids: vessels of the communal gene pool. Philos Trans R Soc Lond B Biol Sci 364:2275–2289. http://dx.doi.org/10.1098/rstb.2009.0037. [PubMed]
23. Thoma L, Muth G. 2015. The conjugative DNA-transfer apparatus of Streptomyces. Int J Med Microbiol 305:224–229. http://dx.doi.org/10.1016/j.ijmm.2014.12.020. [PubMed]
24. Fürste JP, Pansegrau W, Ziegelin G, Kröger M, Lanka E. 1989. Conjugative transfer of promiscuous IncP plasmids: interaction of plasmid-encoded products with the transfer origin. Proc Natl Acad Sci U S A 86:1771–1775. http://dx.doi.org/10.1073/pnas.86.6.1771. [PubMed]
25. Clark AJ, Adelberg EA. 1962. Bacterial conjugation. Annu Rev Microbiol 16:289–319. http://dx.doi.org/10.1146/annurev.mi.16.100162.001445. [PubMed]
26. Christie PJ, Atmakuri K, Krishnamoorthy V, Jakubowski S, Cascales E. 2005. Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu Rev Microbiol 59:451–485. http://dx.doi.org/10.1146/annurev.micro.58.030603.123630. [PubMed]
27. Low HH, Gubellini F, Rivera-Calzada A, Braun N, Connery S, Dujeancourt A, Lu F, Redzej A, Fronzes R, Orlova EV, Waksman G. 2014. Structure of a type IV secretion system. Nature 508:550–553. http://dx.doi.org/10.1038/nature13081. [PubMed]
28. Clarke M, Maddera L, Harris RL, Silverman PM. 2008. F-pili dynamics by live-cell imaging. Proc Natl Acad Sci U S A 105:17978–17981. http://dx.doi.org/10.1073/pnas.0806786105. [PubMed]
29. Cabezón E, Ripoll-Rozada J, Peña A, de la Cruz F, Arechaga I. 2015. Towards an integrated model of bacterial conjugation. FEMS Microbiol Rev 39:81–95. http://dx.doi.org/10.1111/1574-6976.12085. [PubMed]
30. Bradley DE. 1980. Morphological and serological relationships of conjugative pili. Plasmid 4:155–169. http://dx.doi.org/10.1016/0147-619X(80)90005-0. [PubMed]
31. Bradley DE, Taylor DE, Cohen DR. 1980. Specification of surface mating systems among conjugative drug resistance plasmids in Escherichia coli K-12. J Bacteriol 143:1466–1470. [PubMed]
32. del Solar G, Alonso JC, Espinosa M, Díaz-Orejas R. 1996. Broad-host-range plasmid replication: an open question. Mol Microbiol 21:661–666. http://dx.doi.org/10.1046/j.1365-2958.1996.6611376.x. [PubMed]
33. Ghigo JM. 2001. Natural conjugative plasmids induce bacterial biofilm development. Nature 412:442–445. http://dx.doi.org/10.1038/35086581. [PubMed]
34. Garcillán-Barcia MP, Francia MV, de la Cruz F. 2009. The diversity of conjugative relaxases and its application in plasmid classification. FEMS Microbiol Rev 33:657–687. http://dx.doi.org/10.1111/j.1574-6976.2009.00168.x. [PubMed]
35. de la Cruz F, Frost LS, Meyer RJ, Zechner EL. 2010. Conjugative DNA metabolism in Gram-negative bacteria. FEMS Microbiol Rev 34:18–40. http://dx.doi.org/10.1111/j.1574-6976.2009.00195.x. [PubMed]
36. Byrd DR, Matson SW. 1997. Nicking by transesterification: the reaction catalysed by a relaxase. Mol Microbiol 25:1011–1022. http://dx.doi.org/10.1046/j.1365-2958.1997.5241885.x. [PubMed]
37. Guasch A, Lucas M, Moncalián G, Cabezas M, Pérez-Luque R, Gomis-Rüth FX, de la Cruz F, Coll M. 2003. Recognition and processing of the origin of transfer DNA by conjugative relaxase TrwC. Nat Struct Biol 10:1002–1010. http://dx.doi.org/10.1038/nsb1017. [PubMed]
38. Llosa M, Grandoso G, Hernando MA, de la Cruz F. 1996. Functional domains in protein TrwC of plasmid R388: dissected DNA strand transferase and DNA helicase activities reconstitute protein function. J Mol Biol 264:56–67. http://dx.doi.org/10.1006/jmbi.1996.0623. [PubMed]
39. Pansegrau W, Lanka E. 1996. Mechanisms of initiation and termination reactions in conjugative DNA processing. Independence of tight substrate binding and catalytic activity of relaxase (TraI) of IncPα plasmid RP4. J Biol Chem 271:13068–13076. http://dx.doi.org/10.1074/jbc.271.22.13068.
40. Llosa M, Gomis-Rüth FX, Coll M, de la Cruz Fd F. 2002. Bacterial conjugation: a two-step mechanism for DNA transport. Mol Microbiol 45:1–8. http://dx.doi.org/10.1046/j.1365-2958.2002.03014.x. [PubMed]
41. Draper O, César CE, Machón C, de la Cruz F, Llosa M. 2005. Site-specific recombinase and integrase activities of a conjugative relaxase in recipient cells. Proc Natl Acad Sci U S A 102:16385–16390. http://dx.doi.org/10.1073/pnas.0506081102. [PubMed]
42. Garcillán-Barcia MP, Jurado P, González-Pérez B, Moncalián G, Fernández LA, de la Cruz F. 2007. Conjugative transfer can be inhibited by blocking relaxase activity within recipient cells with intrabodies. Mol Microbiol 63:404–416. http://dx.doi.org/10.1111/j.1365-2958.2006.05523.x. [PubMed]
43. Viljanen P, Boratynski J. 1991. The susceptibility of conjugative resistance transfer in gram-negative bacteria to physicochemical and biochemical agents. FEMS Microbiol Rev 8:43–54. [PubMed]
44. van Elsas JD, Fry JC, Hirsch P, Molin S. 2000. Ecology of plasmid transfer and spread, p 175–206. In Thomas CM (ed), The Horizontal Gene Pool: Bacterial Plasmids and Gene Spread. Harwood Academic Publishers, Williston, VT.
45. Aminov RI. 2011. Horizontal gene exchange in environmental microbiota. Front Microbiol 2:158. http://dx.doi.org/10.3389/fmicb.2011.00158. [PubMed]
46. van Elsas JD, Bailey MJ. 2002. The ecology of transfer of mobile genetic elements. FEMS Microbiol Ecol 42:187–197. http://dx.doi.org/10.1111/j.1574-6941.2002.tb01008.x. [PubMed]
47. Koraimann G, Wagner MA. 2014. Social behavior and decision making in bacterial conjugation. Front Cell Infect Microbiol 4:54. http://dx.doi.org/10.3389/fcimb.2014.00054. [PubMed]
48. Chatterjee A, Cook LC, Shu CC, Chen Y, Manias DA, Ramkrishna D, Dunny GM, Hu WS. 2013. Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer. Proc Natl Acad Sci U S A 110:7086–7090. http://dx.doi.org/10.1073/pnas.1212256110. [PubMed]
49. Bertani G, Weigle JJ. 1953. Host controlled variation in bacterial viruses. J Bacteriol 65:113–121. [PubMed]
50. Roberts RJ, Vincze T, Posfai J, Macelis D. 2015. REBAS—a database for DNA restriction and modification: enzymes, genes and genomes. Nucleic Acids Res 43(D1) :D298–D299. http://dx.doi.org/10.1093/nar/gku1046. [PubMed]
51. Vasu K, Nagaraja V. 2013. Diverse functions of restriction-modification systems in addition to cellular defense. Microbiol Mol Biol Rev 77:53–72. http://dx.doi.org/10.1128/MMBR.00044-12. [PubMed]
52. Bickle TA. 2004. Restricting restriction. Mol Microbiol 51:3–5. http://dx.doi.org/10.1046/j.1365-2958.2003.03846.x. [PubMed]
53. Roberts RJ, Belfort M, Bestor T, Bhagwat AS, Bickle TA, Bitinaite J, Blumenthal RM, Degtyarev SK, Dryden DT, Dybvig K, Firman K, Gromova ES, Gumport RI, Halford SE, Hattman S, Heitman J, Hornby DP, Janulaitis A, Jeltsch A, Josephsen J, Kiss A, Klaenhammer TR, Kobayashi I, Kong H, Krüger DH, Lacks S, Marinus MG, Miyahara M, Morgan RD, Murray NE, Nagaraja V, Piekarowicz A, Pingoud A, Raleigh E, Rao DN, Reich N, Repin VE, Selker EU, Shaw PC, Stein DC, Stoddard BL, Szybalski W, Trautner TA, Van Etten JL, Vitor JM, Wilson GG, Xu SY. 2003. A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes. Nucleic Acids Res 31:1805–1812. http://dx.doi.org/10.1093/nar/gkg274. [PubMed]
54. Oliveira PH, Touchon M, Rocha EP. 2014. The interplay of restriction-modification systems with mobile genetic elements and their prokaryotic hosts. Nucleic Acids Res 42:10618–10631. http://dx.doi.org/10.1093/nar/gku734. [PubMed]
55. Kobayashi I. 2001. Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution. Nucleic Acids Res 29:3742–3756. http://dx.doi.org/10.1093/nar/29.18.3742. [PubMed]
56. Samson JE, Magadán AH, Sabri M, Moineau S. 2013. Revenge of the phages: defeating bacterial defences. Nat Rev Microbiol 11:675–687. http://dx.doi.org/10.1038/nrmicro3096. [PubMed]
57. Roer L, Aarestrup FM, Hasman H. 2015. The EcoKI type I restriction-modification system in Escherichia coli affects but is not an absolute barrier for conjugation. J Bacteriol 197:337–342. http://dx.doi.org/10.1128/JB.02418-14. [PubMed]
58. Waldron DE, Lindsay JA. 2006. Sau1: a novel lineage-specific type I restriction-modification system that blocks horizontal gene transfer into Staphylococcus aureus and between S. aureus isolates of different lineages. J Bacteriol 188:5578–5585. http://dx.doi.org/10.1128/JB.00418-06. [PubMed]
59. Pinedo CA, Smets BF. 2005. Conjugal TOL transfer from Pseudomonas putida to Pseudomonas aeruginosa: effects of restriction proficiency, toxicant exposure, cell density ratios, and conjugation detection method on observed transfer efficiencies. Appl Environ Microbiol 71:51–57. http://dx.doi.org/10.1128/AEM.71.1.51-57.2005. [PubMed]
60. Geisenberger O, Ammendola A, Christensen BB, Molin S, Schleifer KH, Eberl L. 1999. Monitoring the conjugal transfer of plasmid RP4 in activated sludge and in situ identification of the transconjugants. FEMS Microbiol Lett 174:9–17. http://dx.doi.org/10.1111/j.1574-6968.1999.tb13543.x. [PubMed]
61. Schäfer A, Kalinowski J, Pühler A. 1994. Increased fertility of Corynebacterium glutamicum recipients in intergeneric matings with Escherichia coli after stress exposure. Appl Environ Microbiol 60:756–759. [PubMed]
62. Trieu-Cuot P, Carlier C, Poyart-Salmeron C, Courvalin P. 1991. Shuttle vectors containing a multiple cloning site and a lacZα gene for conjugal transfer of DNA from Escherichia coli to Gram-positive bacteria. Gene 102:99–104. http://dx.doi.org/10.1016/0378-1119(91)90546-N.
63. Zhou H, Wang Y, Yu Y, Bai T, Chen L, Liu P, Guo H, Zhu C, Tao M, Deng Z. 2012. A non-restricting and non-methylating Escherichia coli strain for DNA cloning and high-throughput conjugation to Streptomyces coelicolor. Curr Microbiol 64:185–190. http://dx.doi.org/10.1007/s00284-011-0048-5. [PubMed]
64. Ohtani N, Sato M, Tomita M, Itaya M. 2008. Restriction on conjugational transfer of pLS20 in Bacillus subtilis 168. Biosci Biotechnol Biochem 72:2472–2475. http://dx.doi.org/10.1271/bbb.80315. [PubMed]
65. Purdy D, O’Keeffe TA, Elmore M, Herbert M, McLeod A, Bokori-Brown M, Ostrowski A, Minton NP. 2002. Conjugative transfer of clostridial shuttle vectors from Escherichia coli to Clostridium difficile through circumvention of the restriction barrier. Mol Microbiol 46:439–452. http://dx.doi.org/10.1046/j.1365-2958.2002.03134.x. [PubMed]
66. Elhai J, Vepritskiy A, Muro-Pastor AM, Flores E, Wolk CP. 1997. Reduction of conjugal transfer efficiency by three restriction activities of Anabaena sp. strain PCC 7120. J Bacteriol 179:1998–2005. http://dx.doi.org/10.1128/jb.179.6.1998-2005.1997. [PubMed]
67. McMahon SA, Roberts GA, Johnson KA, Cooper LP, Liu H, White JH, Carter LG, Sanghvi B, Oke M, Walkinshaw MD, Blakely GW, Naismith JH, Dryden DT. 2009. Extensive DNA mimicry by the ArdA anti-restriction protein and its role in the spread of antibiotic resistance. Nucleic Acids Res 37:4887–4897. http://dx.doi.org/10.1093/nar/gkp478. [PubMed]
68. Wilkins BM. 2002. Plasmid promiscuity: meeting the challenge of DNA immigration control. Environ Microbiol 4:495–500. http://dx.doi.org/10.1046/j.1462-2920.2002.00332.x. [PubMed]
69. Belogurov AA, Delver EP, Agafonova OV, Belogurova NG, Lee LY, Kado CI. 2000. Antirestriction protein Ard (type C) encoded by IncW plasmid pSa has a high similarity to the “protein transport” domain of TraC1 primase of promiscuous plasmid RP4. J Mol Biol 296:969–977. http://dx.doi.org/10.1006/jmbi.1999.3493. [PubMed]
70. Wilkins BM, Chilley PM, Thomas AT, Pocklington MJ. 1996. Distribution of restriction enzyme recognition sequences on broad host range plasmid RP4: molecular and evolutionary implications. J Mol Biol 258:447–456. http://dx.doi.org/10.1006/jmbi.1996.0261. [PubMed]
71. Clewell DB, Weaver KE, Dunny GM, Coque TM, Francia MV, Hayes F. 2014. Extrachromosomal and mobile elements in enterococci: transmission, maintenance, and epidemiology, pp. 309–420. In Gilmore MS, Clewell DB, Ike Y, Shankar N (ed), Enterococci: From Commensals to Leading Causes of Drug Resistant Infection. Boston: Massachusetts Eye and Ear Infirmary.
72. Dupuis ME, Villion M, Magadán AH, Moineau S. 2013. CRISPR-Cas and restriction-modification systems are compatible and increase phage resistance. Nat Commun 4:2087. http://dx.doi.org/10.1038/ncomms3087. [PubMed]
73. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. 2007. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315:1709–1712. http://dx.doi.org/10.1126/science.1138140. [PubMed]
74. Grissa I, Vergnaud G, Pourcel C. 2007. The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats. BMC Bioinformatics 8:172. http://dx.doi.org/10.1186/1471-2105-8-172. [PubMed]
75. Jansen R, Embden JD, Gaastra W, Schouls LM. 2002. Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 43:1565–1575. http://dx.doi.org/10.1046/j.1365-2958.2002.02839.x. [PubMed]
76. Marraffini LA. 2015. CRISPR-Cas immunity in prokaryotes. Nature 526:55–61. http://dx.doi.org/10.1038/nature15386. [PubMed]
77. Andersson AF, Banfield JF. 2008. Virus population dynamics and acquired virus resistance in natural microbial communities. Science 320:1047–1050. http://dx.doi.org/10.1126/science.1157358. [PubMed]
78. Marraffini LA, Sontheimer EJ. 2008. CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322:1843–1845. http://dx.doi.org/10.1126/science.1165771. [PubMed]
79. Makarova KS, Haft DH, Barrangou R, Brouns SJ, Charpentier E, Horvath P, Moineau S, Mojica FJ, Wolf YI, Yakunin AF, van der Oost J, Koonin EV. 2011. Evolution and classification of the CRISPR-Cas systems. Nat Rev Microbiol 9:467–477. http://dx.doi.org/10.1038/nrmicro2577. [PubMed]
80. Sashital DG, Wiedenheft B, Doudna JA. 2012. Mechanism of foreign DNA selection in a bacterial adaptive immune system. Mol Cell 46:606–615. http://dx.doi.org/10.1016/j.molcel.2012.03.020. [PubMed]
81. Marraffini LA, Sontheimer EJ. 2010. Self versus non-self discrimination during CRISPR RNA-directed immunity. Nature 463:568–571. http://dx.doi.org/10.1038/nature08703. [PubMed]
82. Levy A, Goren MG, Yosef I, Auster O, Manor M, Amitai G, Edgar R, Qimron U, Sorek R. 2015. CRISPR adaptation biases explain preference for acquisition of foreign DNA. Nature 520:505–510. http://dx.doi.org/10.1038/nature14302. [PubMed]
83. Sontheimer EJ, Barrangou R. 2015. The bacterial origins of the CRISPR genome-editing revolution. Hum Gene Ther 26:413–424. http://dx.doi.org/10.1089/hum.2015.091. [PubMed]
84. Jiang W, Bikard D, Cox D, Zhang F, Marraffini LA. 2013. RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nat Biotechnol 31:233–239. http://dx.doi.org/10.1038/nbt.2508. [PubMed]
85. Pennisi E. 2013. The CRISPR craze. Science 341:833–836. http://dx.doi.org/10.1126/science.341.6148.833. [PubMed]
86. Westra ER, Staals RH, Gort G, Høgh S, Neumann S, de la Cruz F, Fineran PC, Brouns SJ. 2013. CRISPR-Cas systems preferentially target the leading regions of MOB F conjugative plasmids. RNA Biol 10:749–761. http://dx.doi.org/10.4161/rna.24202. [PubMed]
87. Samson JE, Magadan AH, Moineau S. 2015. The CRISPR-Cas immune system and genetic transfers: reaching an equilibrium. Microbiol Spectr 3:PLAS-0034-2014. http://dx.doi.org/10.1128/microbiolspec.PLAS-0034-2014. [PubMed]
88. Price VJ, Huo W, Sharifi A, Palmer KL. 2016. CRISPR-Cas and restriction-modification act additively against conjugative antibiotic resistance plasmid transfer in Enterococcus faecalis. mSphere 1:e00064-16. http://dx.doi.org/10.1128/mSphere.00064-16. [PubMed]
89. Garneau JE, Dupuis ME, Villion M, Romero DA, Barrangou R, Boyaval P, Fremaux C, Horvath P, Magadán AH, Moineau S. 2010. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 468:67–71. http://dx.doi.org/10.1038/nature09523. [PubMed]
90. Bikard D, Euler CW, Jiang W, Nussenzweig PM, Goldberg GW, Duportet X, Fischetti VA, Marraffini LA. 2014. Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nat Biotechnol 32:1146–1150. http://dx.doi.org/10.1038/nbt.3043. [PubMed]
91. Yosef I, Manor M, Kiro R, Qimron U. 2015. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria. Proc Natl Acad Sci U S A 112:7267–7272. http://dx.doi.org/10.1073/pnas.1500107112. [PubMed]
92. Makarova KS, Wolf YI, van der Oost J, Koonin EV. 2009. Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements. Biol Direct 4:29. http://dx.doi.org/10.1186/1745-6150-4-29. [PubMed]
93. Swarts DC, Jore MM, Westra ER, Zhu Y, Janssen JH, Snijders AP, Wang Y, Patel DJ, Berenguer J, Brouns SJ, van der Oost J. 2014. DNA-guided DNA interference by a prokaryotic Argonaute. Nature 507:258–261. http://dx.doi.org/10.1038/nature12971. [PubMed]
94. Barrangou R, van der Oost J. 2015. Bacteriophage exclusion, a new defense system. EMBO J 34:134–135. http://dx.doi.org/10.15252/embj.201490620. [PubMed]
95. Goldfarb T, Sberro H, Weinstock E, Cohen O, Doron S, Charpak-Amikam Y, Afik S, Ofir G, Sorek R. 2015. BREX is a novel phage resistance system widespread in microbial genomes. EMBO J 34:169–183. http://dx.doi.org/10.15252/embj.201489455. [PubMed]
96. Curtiss R, III, Charamella LJ, Stallions DR, Mays JA. 1968. Parental functions during conjugation in Escherichia coli K-12. Bacteriol Rev 32:320–348. [PubMed]
97. Wilkins BM, Hollom SE. 1974. Conjugational synthesis of F lac + and Col I DNA in the presence of rifampicin and in Escherichia coli K12 mutants defective in DNA synthesis. Mol Gen Genet 134:143–156. http://dx.doi.org/10.1007/BF00268416.
98. Kingsman A, Willetts N. 1978. The requirements for conjugal DNA synthesis in the donor strain during F lac transfer. J Mol Biol 122:287–300. http://dx.doi.org/10.1016/0022-2836(78)90191-2. [PubMed]
99. Lee CA, Babic A, Grossman AD. 2010. Autonomous plasmid-like replication of a conjugative transposon. Mol Microbiol 75:268–279. http://dx.doi.org/10.1111/j.1365-2958.2009.06985.x. [PubMed]
100. Petit MA, Dervyn E, Rose M, Entian KD, McGovern S, Ehrlich SD, Bruand C. 1998. PcrA is an essential DNA helicase of Bacillus subtilis fulfilling functions both in repair and rolling-circle replication. Mol Microbiol 29:261–273. http://dx.doi.org/10.1046/j.1365-2958.1998.00927.x. [PubMed]
101. Tarantino PM, Jr, Zhi C, Wright GE, Brown NC. 1999. Inhibitors of DNA polymerase III as novel antimicrobial agents against gram-positive eubacteria. Antimicrob Agents Chemother 43:1982–1987. [PubMed]
102. Miyazaki R, Minoia M, Pradervand N, Sulser S, Reinhard F, van der Meer JR. 2012. Cellular variability of RpoS expression underlies subpopulation activation of an integrative and conjugative element. PLoS Genet 8:e1002818. http://dx.doi.org/10.1371/journal.pgen.1002818. [PubMed]
103. Roca AI, Cox MM. 1997. RecA protein: structure, function, and role in recombinational DNA repair. Prog Nucleic Acid Res Mol Biol 56:129–223. http://dx.doi.org/10.1016/S0079-6603(08)61005-3. [PubMed]
104. Petrova V, Chitteni-Pattu S, Drees JC, Inman RB, Cox MM. 2009. An SOS inhibitor that binds to free RecA protein: the PsiB protein. Mol Cell 36:121–130. http://dx.doi.org/10.1016/j.molcel.2009.07.026. [PubMed]
105. Baharoglu Z, Bikard D, Mazel D. 2010. Conjugative DNA transfer induces the bacterial SOS response and promotes antibiotic resistance development through integron activation. PLoS Genet 6:e1001165. http://dx.doi.org/10.1371/journal.pgen.1001165. [PubMed]
106. Frost LS, Koraimann G. 2010. Regulation of bacterial conjugation: balancing opportunity with adversity. Future Microbiol 5:1057–1071. http://dx.doi.org/10.2217/fmb.10.70. [PubMed]
107. Fernandez-Lopez R, Del Campo I, Revilla C, Cuevas A, de la Cruz F. 2014. Negative feedback and transcriptional overshooting in a regulatory network for horizontal gene transfer. PLoS Genet 10:e1004171. http://dx.doi.org/10.1371/journal.pgen.1004171. [PubMed]
108. Pérez-Mendoza D, de la Cruz F. 2009. Escherichia coli genes affecting recipient ability in plasmid conjugation: are there any? BMC Genomics 10:71. http://dx.doi.org/10.1186/1471-2164-10-71. [PubMed]
109. Bruand C, Ehrlich SD. 2000. UvrD-dependent replication of rolling-circle plasmids in Escherichia coli. Mol Microbiol 35:204–210. http://dx.doi.org/10.1046/j.1365-2958.2000.01700.x. [PubMed]
110. Watanabe T, Arai T, Hattori T. 1970. Effects of cell wall polysaccharide on the mating ability of Salmonella typhimurium. Nature 225:70–71. http://dx.doi.org/10.1038/225070a0. [PubMed]
111. Monner DA, Jonsson S, Boman HG. 1971. Ampicillin-resistant mutants of Escherichia coli K-12 with lipopolysaccharide alterations affecting mating ability and susceptibility to sex-specific bacteriophages. J Bacteriol 107:420–432. [PubMed]
112. Skurray RA, Hancock RE, Reeves P. 1974. Con – mutants: class of mutants in Escherichia coli K-12 lacking a major cell wall protein and defective in conjugation and adsorption of a bacteriophage. J Bacteriol 119:726–735. [PubMed]
113. Havekes L, Tommassen J, Hoekstra W, Lugtenberg B. 1977. Isolation and characterization of Escherichia coli K-12 F – mutants defective in conjugation with an I-type donor. J Bacteriol 129:1–8. [PubMed]
114. Hoekstra WP, Havekes AM. 1979. On the role of the recipient cell during conjugation in Escherichia coli. Antonie van Leeuwenhoek 45:13–18. http://dx.doi.org/10.1007/BF00400773. [PubMed]
115. Sanderson KE, Janzer J, Head J. 1981. Influence of lipopolysaccharide and protein in the cell envelope on recipient capacity in conjugation of Salmonella typhimurium. J Bacteriol 148:283–293. [PubMed]
116. Manoil C, Rosenbusch JP. 1982. Conjugation-deficient mutants of Escherichia coli distinguish classes of functions of the outer membrane OmpA protein. Mol Gen Genet 187:148–156. http://dx.doi.org/10.1007/BF00384398. [PubMed]
117. Duke J, Guiney DG, Jr. 1983. The role of lipopolysaccharide structure in the recipient cell during plasmid-mediated bacterial conjugation. Plasmid 9:222–226. http://dx.doi.org/10.1016/0147-619X(83)90024-0.
118. Anthony KG, Sherburne C, Sherburne R, Frost LS. 1994. The role of the pilus in recipient cell recognition during bacterial conjugation mediated by F-like plasmids. Mol Microbiol 13:939–953. http://dx.doi.org/10.1111/j.1365-2958.1994.tb00486.x. [PubMed]
119. Ishiwa A, Komano T. 2000. The lipopolysaccharide of recipient cells is a specific receptor for PilV proteins, selected by shufflon DNA rearrangement, in liquid matings with donors bearing the R64 plasmid. Mol Gen Genet 263:159–164. http://dx.doi.org/10.1007/s004380050043. [PubMed]
120. Klimke WA, Rypien CD, Klinger B, Kennedy RA, Rodriguez-Maillard JM, Frost LS. 2005. The mating pair stabilization protein, TraN, of the F plasmid is an outer-membrane protein with two regions that are important for its function in conjugation. Microbiology 151:3527–3540. http://dx.doi.org/10.1099/mic.0.28025-0. [PubMed]
121. Inoue K, Miyazaki R, Ohtsubo Y, Nagata Y, Tsuda M. 2013. Inhibitory effect of Pseudomonas putida nitrogen-related phosphotransferase system on conjugative transfer of IncP-9 plasmid from Escherichia coli. FEMS Microbiol Lett 345:102–109. http://dx.doi.org/10.1111/1574-6968.12188. [PubMed]
122. van Opijnen T, Camilli A. 2013. Transposon insertion sequencing: a new tool for systems-level analysis of microorganisms. Nat Rev Microbiol 11:435–442. http://dx.doi.org/10.1038/nrmicro3033. [PubMed]
123. Johnson CM, Grossman AD. 2014. Identification of host genes that affect acquisition of an integrative and conjugative element in Bacillus subtilis. Mol Microbiol 93:1284–1301. http://dx.doi.org/10.1111/mmi.12736. [PubMed]
124. Bhatty M, Laverde Gomez JA, Christie PJ. 2013. The expanding bacterial type IV secretion lexicon. Res Microbiol 164:620–639. http://dx.doi.org/10.1016/j.resmic.2013.03.012. [PubMed]
125. Lang S, Kirchberger PC, Gruber CJ, Redzej A, Raffl S, Zellnig G, Zangger K, Zechner EL. 2011. An activation domain of plasmid R1 TraI protein delineates stages of gene transfer initiation. Mol Microbiol 82:1071–1085. http://dx.doi.org/10.1111/j.1365-2958.2011.07872.x. [PubMed]
126. Dunny GM. 2013. Enterococcal sex pheromones: signaling, social behavior, and evolution. Annu Rev Genet 47:457–482. http://dx.doi.org/10.1146/annurev-genet-111212-133449. [PubMed]
127. Auchtung JM, Lee CA, Monson RE, Lehman AP, Grossman AD. 2005. Regulation of a Bacillus subtilis mobile genetic element by intercellular signaling and the global DNA damage response. Proc Natl Acad Sci U S A 102:12554–12559. http://dx.doi.org/10.1073/pnas.0505835102. [PubMed]
128. Lederberg J, Cavalli LL, Lederberg EM. 1952. Sex compatibility in Escherichia coli. Genetics 37:720–730. [PubMed]
129. Watanabe T. 1963. Infective heredity of multiple drug resistance in bacteria. Bacteriol Rev 27:87–115. [PubMed]
130. Novick RP. 1969. Extrachromosomal inheritance in bacteria. Bacteriol Rev 33:210–263. [PubMed]
131. Achtman M, Kennedy N, Skurray R. 1977. Cell–cell interactions in conjugating Escherichia coli: role of traT protein in surface exclusion. Proc Natl Acad Sci U S A 74:5104–5108. http://dx.doi.org/10.1073/pnas.74.11.5104. [PubMed]
132. Achtman M, Manning PA, Edelbluth C, Herrlich P. 1979. Export without proteolytic processing of inner and outer membrane proteins encoded by F sex factor tra cistrons in Escherichia coli minicells. Proc Natl Acad Sci U S A 76:4837–4841. http://dx.doi.org/10.1073/pnas.76.10.4837. [PubMed]
133. Klimke WA, Frost LS. 1998. Genetic analysis of the role of the transfer gene, traN, of the F and R100-1 plasmids in mating pair stabilization during conjugation. J Bacteriol 180:4036–4043. [PubMed]
134. Anthony KG, Klimke WA, Manchak J, Frost LS. 1999. Comparison of proteins involved in pilus synthesis and mating pair stabilization from the related plasmids F and R100-1: insights into the mechanism of conjugation. J Bacteriol 181:5149–5159. [PubMed]
135. Audette GF, Manchak J, Beatty P, Klimke WA, Frost LS. 2007. Entry exclusion in F-like plasmids requires intact TraG in the donor that recognizes its cognate TraS in the recipient. Microbiology 153:442–451. http://dx.doi.org/10.1099/mic.0.2006/001917-0. [PubMed]
136. Garcillán-Barcia MP, de la Cruz F. 2008. Why is entry exclusion an essential feature of conjugative plasmids? Plasmid 60:1–18. http://dx.doi.org/10.1016/j.plasmid.2008.03.002. [PubMed]
137. Watanabe T, Fukasawa T. 1962. Episome-mediated transfer of drug resistance in Enterobacteriaceae. IV. Interactions between resistance transfer factor and F-factor in Escherichia coli K-12. J Bacteriol 83:727–735. [PubMed]
138. Koraimann G, Teferle K, Markolin G, Woger W, Högenauer G. 1996. The FinOP repressor system of plasmid R1: analysis of the antisense RNA control of traJ expression and conjugative DNA transfer. Mol Microbiol 21:811–821. http://dx.doi.org/10.1046/j.1365-2958.1996.361401.x. [PubMed]
139. Jerome LJ, van Biesen T, Frost LS. 1999. Degradation of FinP antisense RNA from F-like plasmids: the RNA-binding protein, FinO, protects FinP from ribonuclease E. J Mol Biol 285:1457–1473. http://dx.doi.org/10.1006/jmbi.1998.2404. [PubMed]
140. Jerome LJ, Frost LS. 1999. In vitro analysis of the interaction between the FinO protein and FinP antisense RNA of F-like conjugative plasmids. J Biol Chem 274:10356–10362. http://dx.doi.org/10.1074/jbc.274.15.10356. [PubMed]
141. Frost LS, Ippen-Ihler K, Skurray RA. 1994. Analysis of the sequence and gene products of the transfer region of the F sex factor. Microbiol Rev 58:162–210. [PubMed]
142. Gasson MJ, Willetts NS. 1977. Further characterization of the F fertility inhibition systems of “unusual” Fin + plasmids. J Bacteriol 131:413–420. [PubMed]
143. Gasson MJ, Willetts NS. 1975. Five control systems preventing transfer of Escherichia coli K-12 sex factor F. J Bacteriol 122:518–525. [PubMed]
144. Gasson M, Willetts N. 1976. Transfer gene expression during fertility inhibition of the Escherichia coli K12 sex factor F by the I-like plasmid R62. Mol Gen Genet 149:329–333. http://dx.doi.org/10.1007/BF00268535. [PubMed]
145. Gaffney D, Skurray R, Willetts N, Brenner S. 1983. Regulation of the F conjugation genes studied by hybridization and tra-lacZ fusion. J Mol Biol 168:103–122. http://dx.doi.org/10.1016/S0022-2836(83)80325-8. [PubMed]
146. Ham LM, Skurray R. 1989. Molecular analysis and nucleotide sequence of finQ, a transcriptional inhibitor of the F plasmid transfer genes. Mol Gen Genet 216:99–105. http://dx.doi.org/10.1007/BF00332236.
147. Penfold SS, Simon J, Frost LS. 1996. Regulation of the expression of the traM gene of the F sex factor of Escherichia coli. Mol Microbiol 20:549–558. http://dx.doi.org/10.1046/j.1365-2958.1996.5361059.x. [PubMed]
148. Willetts N. 1980. Interactions between the F conjugal transfer system and CloDF13::Tna plasmids. Mol Gen Genet 180:213–217. http://dx.doi.org/10.1007/BF00267372. [PubMed]
149. Olsen RH, Shipley PL. 1975. RP1 properties and fertility inhibition among P, N, W, and X incompatibility group plasmids. J Bacteriol 123:28–35. [PubMed]
150. Yusoff K, Stanisich VA. 1984. Location of a function on RP1 that fertility inhibits Inc W plasmids. Plasmid 11:178–181. http://dx.doi.org/10.1016/0147-619X(84)90022-2.
151. Fong ST, Stanisich VA. 1989. Location and characterization of two functions on RP1 that inhibit the fertility of the IncW plasmid R388. J Gen Microbiol 135:499–502. [PubMed]
152. Pinney RJ, Smith JT. 1974. Fertility inhibition of an N group R factor by a group X R factor, R6K. J Gen Microbiol 82:415–418. http://dx.doi.org/10.1099/00221287-82-2-415. [PubMed]
153. Herrera-Cervera JA, Olivares J, Sanjuan J. 1996. Ammonia inhibition of plasmid pRmeGR4a conjugal transfer between Rhizobium meliloti strains. Appl Environ Microbiol 62:1145–1150. [PubMed]
154. Datta N, Hedges RW, Shaw EJ, Sykes RB, Richmond MH. 1971. Properties of an R factor from Pseudomonas aeruginosa. J Bacteriol 108:1244–1249. [PubMed]
155. Coetzee JN, Datta N, Hedges RW. 1972. R factors from Proteus rettgeri. J Gen Microbiol 72:543–552. http://dx.doi.org/10.1099/00221287-72-3-543. [PubMed]
156. Winans SC, Walker GC. 1985. Fertility inhibition of RP1 by IncN plasmid pKM101. J Bacteriol 161:425–427. [PubMed]
157. Tanimoto K, Iino T. 1983. Transfer inhibition of RP4 by F factor. Mol Gen Genet 192:104–109. http://dx.doi.org/10.1007/BF00327654. [PubMed]
158. Tanimoto K, Iino T. 1984. An essential gene for replication of the mini-F plasmid from origin I. Mol Gen Genet 196:59–63. http://dx.doi.org/10.1007/BF00334092. [PubMed]
159. Miller JF, Malamy MH. 1983. Identification of the pifC gene and its role in negative control of F factor pif gene expression. J Bacteriol 156:338–347. [PubMed]
160. Miller JF, Lanka E, Malamy MH. 1985. F factor inhibition of conjugal transfer of broad-host-range plasmid RP4: requirement for the protein product of pif operon regulatory gene pifC. J Bacteriol 163:1067–1073. [PubMed]
161. Tanimoto K, Iino T, Ohtsubo H, Ohtsubo E. 1985. Identification of a gene, tir of R100, functionally homologous to the F3 gene of F in the inhibition of RP4 transfer. Mol Gen Genet 198:356–357. http://dx.doi.org/10.1007/BF00383019. [PubMed]
162. Santini JM, Stanisich VA. 1998. Both the fipA gene of pKM101 and the pifC gene of F inhibit conjugal transfer of RP1 by an effect on traG. J Bacteriol 180:4093–4101. [PubMed]
163. Loper JE, Kado CI. 1979. Host range conferred by the virulence-specifying plasmid of Agrobacterium tumefaciens. J Bacteriol 139:591–596. [PubMed]
164. Farrand S, Kado C, Ireland C. 1981. Suppression of tumorigenicity by the IncW R plasmid pSa in Agrobacterium tumefaciens. Mol Gen Genet 181:44–51. http://dx.doi.org/10.1007/BF00339003.
165. Close SM, Kado CI. 1991. The osa gene of pSa encodes a 21.1-kilodalton protein that suppresses Agrobacterium tumefaciens oncogenicity. J Bacteriol 173:5449–5456. http://dx.doi.org/10.1128/jb.173.17.5449-5456.1991. [PubMed]
166. Ward JE, Jr, Dale EM, Binns AN. 1991. Activity of the Agrobacterium T-DNA transfer machinery is affected by virB gene products. Proc Natl Acad Sci U S A 88:9350–9354. http://dx.doi.org/10.1073/pnas.88.20.9350. [PubMed]
167. Binns AN, Beaupré CE, Dale EM. 1995. Inhibition of VirB-mediated transfer of diverse substrates from Agrobacterium tumefaciens by the IncQ plasmid RSF1010. J Bacteriol 177:4890–4899. http://dx.doi.org/10.1128/jb.177.17.4890-4899.1995. [PubMed]
168. Stahl LE, Jacobs A, Binns AN. 1998. The conjugal intermediate of plasmid RSF1010 inhibits Agrobacterium tumefaciens virulence and VirB-dependent export of VirE2. J Bacteriol 180:3933–3939. [PubMed]
169. Lee LY, Gelvin SB. 2004. Osa protein constitutes a strong oncogenic suppression system that can block vir-dependent transfer of IncQ plasmids between Agrobacterium cells and the establishment of IncQ plasmids in plant cells. J Bacteriol 186:7254–7261. http://dx.doi.org/10.1128/JB.186.21.7254-7261.2004. [PubMed]
170. Chen CY, Kado CI. 1994. Inhibition of Agrobacterium tumefaciens oncogenicity by the osa gene of pSa. J Bacteriol 176:5697–5703. http://dx.doi.org/10.1128/jb.176.18.5697-5703.1994. [PubMed]
171. Chen CY, Kado CI. 1996. Osa protein encoded by plasmid pSa is located at the inner membrane but does not inhibit membrane association of VirB and VirD virulence proteins in Agrobacterium tumefaciens. FEMS Microbiol Lett 135:85–92. http://dx.doi.org/10.1111/j.1574-6968.1996.tb07970.x.
172. Lee LY, Gelvin SB, Kado CI. 1999. pSa causes oncogenic suppression of Agrobacterium by inhibiting VirE2 protein export. J Bacteriol 181:186–196. [PubMed]
173. Chumakov MI. 2013. Protein apparatus for horizontal transfer of agrobacterial T-DNA to eukaryotic cells. Biochemistry (Mosc) 78:1321–1332. http://dx.doi.org/10.1134/S000629791312002X. [PubMed]
174. Schrammeijer B, den Dulk-Ras A, Vergunst AC, Jurado Jácome E, Hooykaas PJ. 2003. Analysis of Vir protein translocation from Agrobacterium tumefaciens using Saccharomyces cerevisiae as a model: evidence for transport of a novel effector protein VirE3. Nucleic Acids Res 31:860–868. http://dx.doi.org/10.1093/nar/gkg179. [PubMed]
175. Cascales E, Atmakuri K, Liu Z, Binns AN, Christie PJ. 2005. Agrobacterium tumefaciens oncogenic suppressors inhibit T-DNA and VirE2 protein substrate binding to the VirD4 coupling protein. Mol Microbiol 58:565–579. http://dx.doi.org/10.1111/j.1365-2958.2005.04852.x. [PubMed]
176. Maindola P, Raina R, Goyal P, Atmakuri K, Ojha A, Gupta S, Christie PJ, Iyer LM, Aravind L, Arockiasamy A. 2014. Multiple enzymatic activities of ParB/Srx superfamily mediate sexual conflict among conjugative plasmids. Nat Commun 5:5322. http://dx.doi.org/10.1038/ncomms6322. [PubMed]
177. Fernandez-Lopez R, Machón C, Longshaw CM, Martin S, Molin S, Zechner EL, Espinosa M, Lanka E, de la Cruz F. 2005. Unsaturated fatty acids are inhibitors of bacterial conjugation. Microbiology 151:3517–3526. http://dx.doi.org/10.1099/mic.0.28216-0. [PubMed]
178. Lujan SA, Guogas LM, Ragonese H, Matson SW, Redinbo MR. 2007. Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase. Proc Natl Acad Sci U S A 104:12282–12287. http://dx.doi.org/10.1073/pnas.0702760104. [PubMed]
179. Nash RP, McNamara DE, Ballentine WK, III, Matson SW, Redinbo MR. 2012. Investigating the impact of bisphosphonates and structurally related compounds on bacteria containing conjugative plasmids. Biochem Biophys Res Commun 424:697–703. http://dx.doi.org/10.1016/j.bbrc.2012.07.012. [PubMed]
180. Jalasvuori M, Friman VP, Nieminen A, Bamford JK, Buckling A. 2011. Bacteriophage selection against a plasmid-encoded sex apparatus leads to the loss of antibiotic-resistance plasmids. Biol Lett 7:902–905. http://dx.doi.org/10.1098/rsbl.2011.0384. [PubMed]
181. Ojala V, Laitalainen J, Jalasvuori M. 2013. Fight evolution with evolution: plasmid-dependent phages with a wide host range prevent the spread of antibiotic resistance. Evol Appl 6:925–932. http://dx.doi.org/10.1111/eva.12076. [PubMed]
182. Harrison E, Wood AJ, Dytham C, Pitchford JW, Truman J, Spiers A, Paterson S, Brockhurst MA. 2015. Bacteriophages limit the existence conditions for conjugative plasmids. mBio 6:e00586. http://dx.doi.org/10.1128/mBio.00586-15. [PubMed]
183. Hagens S, Habel A, Bläsi U. 2006. Augmentation of the antimicrobial efficacy of antibiotics by filamentous phage. Microb Drug Resist 12:164–168. http://dx.doi.org/10.1089/mdr.2006.12.164. [PubMed]
184. Boeke JD, Model P, Zinder ND. 1982. Effects of bacteriophage f1 gene III protein on the host cell membrane. Mol Gen Genet 186:185–192. http://dx.doi.org/10.1007/BF00331849. [PubMed]
185. Brinton CC, Jr, Gemski P, Jr, Carnahan J. 1964. A new type of bacterial pilus genetically controlled by the fertility factor of E. coli K 12 and its role in chromosome transfer. Proc Natl Acad Sci U S A 52:776–783. http://dx.doi.org/10.1073/pnas.52.3.776. [PubMed]
186. Knolle P. 1967. Evidence for the identity of the mating-specific site of male cells of Escherichia coli with the receptor site of an RNA phage. Biochem Biophys Res Commun 27:81–87. http://dx.doi.org/10.1016/S0006-291X(67)80043-3.
187. Ippen KA, Valentine RC. 1967. The sex hair of E. coli as sensory fiber, conjugation tube, or mating arm? Biochem Biophys Res Commun 27:674–680. http://dx.doi.org/10.1016/S0006-291X(67)80088-3. [PubMed]
188. Novotny C, Knight WS, Brinton CC, Jr. 1968. Inhibition of bacterial conjugation by ribonucleic acid and deoxyribonucleic acid male-specific bacteriophages. J Bacteriol 95:314–326. [PubMed]
189. Salzman TC. 1971. Coordination of sex pili with their specifying R factors. Nat New Biol 230:278–279. http://dx.doi.org/10.1038/newbio230278a0. [PubMed]
190. Ou JT. 1973. Inhibition of formation of Escherichia coli mating pairs by f1 and MS2 bacteriophages as determined with a Coulter counter. J Bacteriol 114:1108–1115. [PubMed]
191. Schreil W, Christensen JR. 1974. Conjugation and phage MS 2 infection with Hfr Escherichia coli. Arch Mikrobiol 95:19–28. http://dx.doi.org/10.1007/BF02451744. [PubMed]
192. Lin A, Jimenez J, Derr J, Vera P, Manapat ML, Esvelt KM, Villanueva L, Liu DR, Chen IA. 2011. Inhibition of bacterial conjugation by phage M13 and its protein g3p: quantitative analysis and model. PLoS One 6:e19991. http://dx.doi.org/10.1371/journal.pone.0019991. [PubMed]
193. Lubkowski J, Hennecke F, Plückthun A, Wlodawer A. 1999. Filamentous phage infection: crystal structure of g3p in complex with its coreceptor, the C-terminal domain of TolA. Structure 7:711–722. http://dx.doi.org/10.1016/S0969-2126(99)80092-6.
194. Wan Z, Goddard NL. 2012. Competition between conjugation and M13 phage infection in Escherichia coli in the absence of selection pressure: a kinetic study. G3 (Bethesda) 2:1137–1144. http://dx.doi.org/10.1534/g3.112.003418. [PubMed]
195. Freese PD, Korolev KS, Jiménez JI, Chen IA. 2014. Genetic drift suppresses bacterial conjugation in spatially structured populations. Biophys J 106:944–954. http://dx.doi.org/10.1016/j.bpj.2014.01.012. [PubMed]
196. May T, Tsuruta K, Okabe S. 2011. Exposure of conjugative plasmid carrying Escherichia coli biofilms to male-specific bacteriophages. ISME J 5:771–775. http://dx.doi.org/10.1038/ismej.2010.158. [PubMed]
197. Harden V, Meynell E. 1972. Inhibition of gene transfer by antiserum and identification of serotypes of sex pili. J Bacteriol 109:1067–1074. [PubMed]
198. Lawn AM, Meynell E. 1970. Serotypes of sex pili. J Hyg (Lond) 68:683–694. http://dx.doi.org/10.1017/S0022172400042625. [PubMed]
199. Tzagoloff H, Pratt D. 1964. The initial steps in infection with coliphage M13. Virology 24:372–380. http://dx.doi.org/10.1016/0042-6822(64)90174-6. [PubMed]
200. Ou JT, Anderson TF. 1972. Effect of Zn 2+ on bacterial conjugation: inhibition of mating pair formation. J Bacteriol 111:177–185. [PubMed]
201. Ou JT. 1973. Effect of Zn 2+ on bacterial conjugation: increase in ability of F – cells to form mating pairs. J Bacteriol 115:648–654. [PubMed]
202. Ou JT, Reim R. 1976. Effect of 1,10-phenanthroline on bacterial conjugation in Escherichia coli K-12: inhibition of maturation from preliminary mates into effective mates. J Bacteriol 128:363–371. [PubMed]
203. Sneath PH, Lederberg J. 1961. Inhibition by periodate of mating in Escherichia coli K-12. Proc Natl Acad Sci U S A 47:86–90. http://dx.doi.org/10.1073/pnas.47.1.86. [PubMed]
204. Dettori R, Maccacaro G, Piccinin G. 1961. Sex-specific bacteriophages of Escherichia coli K12. G Microbiol 9:141–150.
205. Raab C, Röschenthaler R. 1970. Inhibition of adsorption and replication of the RNA-phage MS-2 in Escherichia coli C 3000 by levallorphan. Biochem Biophys Res Commun 41:1429–1436. http://dx.doi.org/10.1016/0006-291X(70)90546-2.
206. Löser R, Boquet PL, Röschenthaler R. 1971. Inhibition of R-factor transfer by levallorphan. Biochem Biophys Res Commun 45:204–211. http://dx.doi.org/10.1016/0006-291X(71)90070-2.
207. Mándi Y, Molnár J. 1981. Effect of chlorpromazine on conjugal plasmid transfer and sex pili. Acta Microbiol Acad Sci Hung 28:205–210. [PubMed]
208. Singleton P. 1983. Colloidal clay inhibits conjugal transfer of R-plasmid R1 drd-19 in Escherichia coli. Appl Environ Microbiol 46:756–757. [PubMed]
209. Roper MM, Marshall KC. 1977. Effects of a clay mineral on microbial predation and parasitism of Escherichia coli. Microb Ecol 4:279–289. http://dx.doi.org/10.1007/BF02013272. [PubMed]
210. Roper MM, Marshall KC. 1978. Effect of clay particle size on clay- Escherichia coli-bacteriophage interactions. Microbiology 106:187–189.
211. Qiu Z, Yu Y, Chen Z, Jin M, Yang D, Zhao Z, Wang J, Shen Z, Wang X, Qian D, Huang A, Zhang B, Li JW. 2012. Nanoalumina promotes the horizontal transfer of multiresistance genes mediated by plasmids across genera. Proc Natl Acad Sci U S A 109:4944–4949. http://dx.doi.org/10.1073/pnas.1107254109. [PubMed]
212. Schwartz GH, Eiler D, Kern M. 1965. Solubilization of the conjugation inhibitor from Escherichia coli cell wall. J Bacteriol 89:89–94. [PubMed]
213. Lancaster JH, Goldschmidt EP, Wyss O. 1965. Characterization of conjugation factors in Escherichia coli cell walls. I. Inhibition of recombination by cell walls and cell extracts. J Bacteriol 89:1478–1481. [PubMed]
214. Spengler G, Molnár A, Schelz Z, Amaral L, Sharples D, Molnár J. 2006. The mechanism of plasmid curing in bacteria. Curr Drug Targets 7:823–841. http://dx.doi.org/10.2174/138945006777709601. [PubMed]
215. Bidlack JE, Silverman PM. 2004. An active type IV secretion system encoded by the F plasmid sensitizes Escherichia coli to bile salts. J Bacteriol 186:5202–5209. http://dx.doi.org/10.1128/JB.186.16.5202-5209.2004. [PubMed]
216. Daugelavicius R, Bamford JK, Grahn AM, Lanka E, Bamford DH. 1997. The IncP plasmid-encoded cell envelope-associated DNA transfer complex increases cell permeability. J Bacteriol 179:5195–5202. http://dx.doi.org/10.1128/jb.179.16.5195-5202.1997. [PubMed]
217. Russell AB, Peterson SB, Mougous JD. 2014. Type VI secretion system effectors: poisons with a purpose. Nat Rev Microbiol 12:137–148. http://dx.doi.org/10.1038/nrmicro3185. [PubMed]
218. Basler M, Ho BT, Mekalanos JJ. 2013. Tit-for-tat: type VI secretion system counterattack during bacterial cell-cell interactions. Cell 152:884–894. http://dx.doi.org/10.1016/j.cell.2013.01.042. [PubMed]
219. Ho BT, Basler M, Mekalanos JJ. 2013. Type 6 secretion system-mediated immunity to type 4 secretion system-mediated gene transfer. Science 342:250–253. http://dx.doi.org/10.1126/science.1243745. [PubMed]
220. Weisser J, Wiedemann B. 1987. Inhibition of R-plasmid transfer in Escherichia coli by 4-quinolones. Antimicrob Agents Chemother 31:531–534. http://dx.doi.org/10.1128/AAC.31.4.531. [PubMed]
221. Debbia EA, Massaro S, Campora U, Schito GC. 1994. Inhibition of F’lac transfer by various antibacterial drugs in Escherichia coli. New Microbiol 17:65–68. [PubMed]
222. Michel-Briand Y, Laporte JM. 1985. Inhibition of conjugal transfer of R plasmids by nitrofurans. J Gen Microbiol 131:2281–2284.
223. Nakamura S, Inoue S, Shimizu M, Iyobe S, Mitsuhashi S. 1976. Inhibition of conjugal transfer of R plasmids by pipemidic acid and related compounds. Antimicrob Agents Chemother 10:779–785. http://dx.doi.org/10.1128/AAC.10.5.779. [PubMed]
224. Warnes SL, Highmore CJ, Keevil CW. 2012. Horizontal transfer of antibiotic resistance genes on abiotic touch surfaces: implications for public health. mBio 3:e00489-12. http://dx.doi.org/10.1128/mBio.00489-12. [PubMed]
225. Warnes SL, Green SM, Michels HT, Keevil CW. 2010. Biocidal efficacy of copper alloys against pathogenic enterococci involves degradation of genomic and plasmid DNAs. Appl Environ Microbiol 76:5390–5401. http://dx.doi.org/10.1128/AEM.03050-09. [PubMed]
226. Warnes SL, Caves V, Keevil CW. 2012. Mechanism of copper surface toxicity in Escherichia coli O157:H7 and Salmonella involves immediate membrane depolarization followed by slower rate of DNA destruction which differs from that observed for Gram-positive bacteria. Environ Microbiol 14:1730–1743. http://dx.doi.org/10.1111/j.1462-2920.2011.02677.x. [PubMed]
227. Hong R, Kang TY, Michels CA, Gadura N. 2012. Membrane lipid peroxidation in copper alloy-mediated contact killing of Escherichia coli. Appl Environ Microbiol 78:1776–1784. http://dx.doi.org/10.1128/AEM.07068-11. [PubMed]
228. Zhao WH, Hu ZQ, Hara Y, Shimamura T. 2001. Inhibition by epigallocatechin gallate (EGCg) of conjugative R plasmid transfer in Escherichia coli. J Infect Chemother 7:195–197. http://dx.doi.org/10.1007/s101560100035. [PubMed]
229. Oyedemi BO, Shinde V, Shinde K, Kakalou D, Stapleton PD, Gibbons S. 2016. Novel R-plasmid conjugal transfer inhibitory and antibacterial activities of phenolic compounds from Mallotus philippensis (Lam.) Mull. Arg. J Glob Antimicrob Resist 5:15–21. http://dx.doi.org/10.1016/j.jgar.2016.01.011. [PubMed]
230. Emeruwa AC. 1982. Antibacterial substance from Carica papaya fruit extract. J Nat Prod 45:123–127. http://dx.doi.org/10.1021/np50020a002. [PubMed]
231. Leite AA, Nardi RM, Nicoli JR, Chartone-Souza E, Nascimento AM. 2005. Carica papaya seed macerate as inhibitor of conjugative R plasmid transfer from Salmonella typhimurium to Escherichia coli in vitro and in the digestive tract of gnotobiotic mice. J Gen Appl Microbiol 51:21–26. http://dx.doi.org/10.2323/jgam.51.21. [PubMed]
232. García-Quintanilla M, Ramos-Morales F, Casadesús J. 2008. Conjugal transfer of the Salmonella enterica virulence plasmid in the mouse intestine. J Bacteriol 190:1922–1927. http://dx.doi.org/10.1128/JB.01626-07. [PubMed]
233. Heseltine WW, Galloway LD. 1951. Some antibacterial properties of sodium propionate. J Pharm Pharmacol 3:581–585. http://dx.doi.org/10.1111/j.2042-7158.1951.tb13103.x. [PubMed]
234. Couce A, Blázquez J. 2009. Side effects of antibiotics on genetic variability. FEMS Microbiol Rev 33:531–538. http://dx.doi.org/10.1111/j.1574-6976.2009.00165.x. [PubMed]
235. Beaber JW, Hochhut B, Waldor MK. 2004. SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature 427:72–74. http://dx.doi.org/10.1038/nature02241. [PubMed]
236. Stevens AM, Shoemaker NB, Li LY, Salyers AA. 1993. Tetracycline regulation of genes on Bacteroides conjugative transposons. J Bacteriol 175:6134–6141. http://dx.doi.org/10.1128/jb.175.19.6134-6141.1993. [PubMed]
237. Torres OR, Korman RZ, Zahler SA, Dunny GM. 1991. The conjugative transposon Tn 925: enhancement of conjugal transfer by tetracycline in Enterococcus faecalis and mobilization of chromosomal genes in Bacillus subtilis and E. faecalis. Mol Gen Genet 225:395–400. http://dx.doi.org/10.1007/BF00261679. [PubMed]
238. Barr V, Barr K, Millar MR, Lacey RW. 1986. Beta-lactam antibiotics increase the frequency of plasmid transfer in Staphylococcus aureus. J Antimicrob Chemother 17:409–413. http://dx.doi.org/10.1093/jac/17.4.409. [PubMed]
239. Francia MV, Varsaki A, Garcillán-Barcia MP, Latorre A, Drainas C, de la Cruz F. 2004. A classification scheme for mobilization regions of bacterial plasmids. FEMS Microbiol Rev 28:79–100. http://dx.doi.org/10.1016/j.femsre.2003.09.001. [PubMed]
240. Getino M, Fernández-López R, Palencia-Gándara C, Campos-Gómez J, Sánchez-López JM, Martínez M, Fernández A, de la Cruz F. 2016. Tanzawaic acids, a chemically novel set of bacterial conjugation inhibitors. PLoS One 11:e0148098. http://dx.doi.org/10.1371/journal.pone.0148098. [PubMed]
241. Getino M, Sanabria-Ríos DJ, Fernández-López R, Campos-Gómez J, Sánchez-López JM, Fernández A, Carballeira NM, de la Cruz F. 2015. Synthetic fatty acids prevent plasmid-mediated horizontal gene transfer. mBio 6:e01032-e15. http://dx.doi.org/10.1128/mBio.01032-15. [PubMed]
242. Carattoli A. 2009. Resistance plasmid families in Enterobacteriaceae. Antimicrob Agents Chemother 53:2227–2238. http://dx.doi.org/10.1128/AAC.01707-08. [PubMed]
243. Ripoll-Rozada J, García-Cazorla Y, Getino M, Machón C, Sanabria-Ríos D, de la Cruz F, Cabezón E, Arechaga I. 2016. Type IV traffic ATPase TrwD as molecular target to inhibit bacterial conjugation. Mol Microbiol 100:912–921. http://dx.doi.org/10.1111/mmi.13359. [PubMed]
244. Kerr JE, Christie PJ. 2010. Evidence for VirB4-mediated dislocation of membrane-integrated VirB2 pilin during biogenesis of the Agrobacterium VirB/VirD4 type IV secretion system. J Bacteriol 192:4923–4934. http://dx.doi.org/10.1128/JB.00557-10. [PubMed]
245. Atmakuri K, Cascales E, Christie PJ. 2004. Energetic components VirD4, VirB11 and VirB4 mediate early DNA transfer reactions required for bacterial type IV secretion. Mol Microbiol 54:1199–1211. http://dx.doi.org/10.1111/j.1365-2958.2004.04345.x. [PubMed]
246. Guglielmini J, Néron B, Abby SS, Garcillán-Barcia MP, de la Cruz F, Rocha EP. 2014. Key components of the eight classes of type IV secretion systems involved in bacterial conjugation or protein secretion. Nucleic Acids Res 42:5715–5727. http://dx.doi.org/10.1093/nar/gku194. [PubMed]
247. Hilleringmann M, Pansegrau W, Doyle M, Kaufman S, MacKichan ML, Gianfaldoni C, Ruggiero P, Covacci A. 2006. Inhibitors of Helicobacter pylori ATPase Cagα block CagA transport and cag virulence. Microbiology 152:2919–2930. http://dx.doi.org/10.1099/mic.0.28984-0. [PubMed]
248. Sayer JR, Walldén K, Pesnot T, Campbell F, Gane PJ, Simone M, Koss H, Buelens F, Boyle TP, Selwood DL, Waksman G, Tabor AB. 2014. 2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion. Bioorg Med Chem 22:6459–6470. http://dx.doi.org/10.1016/j.bmc.2014.09.036. [PubMed]
249. Shaffer CL, Good JA, Kumar S, Krishnan KS, Gaddy JA, Loh JT, Chappell J, Almqvist F, Cover TL, Hadjifrangiskou M. 2016. Peptidomimetic small molecules disrupt type IV secretion system activity in diverse bacterial pathogens. mBio 7:e00221-e16. http://dx.doi.org/10.1128/mBio.00221-16. [PubMed]
250. Pinkner JS, Remaut H, Buelens F, Miller E, Aberg V, Pemberton N, Hedenström M, Larsson A, Seed P, Waksman G, Hultgren SJ, Almqvist F. 2006. Rationally designed small compounds inhibit pilus biogenesis in uropathogenic bacteria. Proc Natl Acad Sci U S A 103:17897–17902. http://dx.doi.org/10.1073/pnas.0606795103. [PubMed]
251. Galán JE, Lara-Tejero M, Marlovits TC, Wagner S. 2014. Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu Rev Microbiol 68:415–438. http://dx.doi.org/10.1146/annurev-micro-092412-155725. [PubMed]
252. Charro N, Mota LJ. 2015. Approaches targeting the type III secretion system to treat or prevent bacterial infections. Expert Opin Drug Discov 10:373–387. http://dx.doi.org/10.1517/17460441.2015.1019860. [PubMed]
253. Felise HB, Nguyen HV, Pfuetzner RA, Barry KC, Jackson SR, Blanc MP, Bronstein PA, Kline T, Miller SI. 2008. An inhibitor of Gram-negative bacterial virulence protein secretion. Cell Host Microbe 4:325–336. http://dx.doi.org/10.1016/j.chom.2008.08.001. [PubMed]
254. Krüger DH, Barcak GJ, Reuter M, Smith HO. 1988. EcoRII can be activated to cleave refractory DNA recognition sites. Nucleic Acids Res 16:3997–4008. http://dx.doi.org/10.1093/nar/16.9.3997. [PubMed]
255. Meisel A, Bickle TA, Krüger DH, Schroeder C. 1992. Type III restriction enzymes need two inversely oriented recognition sites for DNA cleavage. Nature 355:467–469. http://dx.doi.org/10.1038/355467a0. [PubMed]
256. Warren RA. 1980. Modified bases in bacteriophage DNAs. Annu Rev Microbiol 34:137–158. http://dx.doi.org/10.1146/annurev.mi.34.100180.001033. [PubMed]
257. Iida S, Streiff MB, Bickle TA, Arber W. 1987. Two DNA antirestriction systems of bacteriophage P1, darA, and darB: characterization of darA – phages. Virology 157:156–166. http://dx.doi.org/10.1016/0042-6822(87)90324-2.
258. Zabeau M, Friedman S, Van Montagu M, Schell J. 1980. The ral gene of phage lambda. I. Identification of a non-essential gene that modulates restriction and modification in E. coli. Mol Gen Genet 179:63–73. http://dx.doi.org/10.1007/BF00268447. [PubMed]
259. Studier FW, Movva NR. 1976. SAMase gene of bacteriophage T3 is responsible for overcoming host restriction. J Virol 19:136–145. [PubMed]
260. Walkinshaw MD, Taylor P, Sturrock SS, Atanasiu C, Berge T, Henderson RM, Edwardson JM, Dryden DT. 2002. Structure of Ocr from bacteriophage T7, a protein that mimics B-form DNA. Mol Cell 9:187–194. http://dx.doi.org/10.1016/S1097-2765(02)00435-5.
261. Serna A, Espinosa E, Camacho EM, Casadesús J. 2010. Regulation of bacterial conjugation in microaerobiosis by host-encoded functions ArcAB and sdhABCD. Genetics 184:947–958. http://dx.doi.org/10.1534/genetics.109.109918. [PubMed]
262. Camacho EM, Serna A, Casadesús J. 2005. Regulation of conjugal transfer by Lrp and Dam methylation in plasmid R100. Int Microbiol 8:279–285. [PubMed]
263. Will WR, Lu J, Frost LS. 2004. The role of H-NS in silencing F transfer gene expression during entry into stationary phase. Mol Microbiol 54:769–782. http://dx.doi.org/10.1111/j.1365-2958.2004.04303.x. [PubMed]
264. Shin M, Song M, Rhee JH, Hong Y, Kim YJ, Seok YJ, Ha KS, Jung SH, Choy HE. 2005. DNA looping-mediated repression by histone-like protein H-NS: specific requirement of Eσ 70 as a cofactor for looping. Genes Dev 19:2388–2398. http://dx.doi.org/10.1101/gad.1316305. [PubMed]
265. Wada C, Imai M, Yura T. 1987. Host control of plasmid replication: requirement for the σ factor σ 32 in transcription of mini-F replication initiator gene. Proc Natl Acad Sci U S A 84:8849–8853. http://dx.doi.org/10.1073/pnas.84.24.8849. [PubMed]
266. Dorman CJ. 2009. Nucleoid-associated proteins and bacterial physiology. Adv Appl Microbiol 67:47–64. http://dx.doi.org/10.1016/S0065-2164(08)01002-2. [PubMed]
267. Gamas P, Caro L, Galas D, Chandler M. 1987. Expression of F transfer functions depends on the Escherichia coli integration host factor. Mol Gen Genet 207:302–305. http://dx.doi.org/10.1007/BF00331593. [PubMed]
268. Starcic M, Zgur-Bertok D, Jordi BJ, Wösten MM, Gaastra W, van Putten JP. 2003. The cyclic AMP-cyclic AMP receptor protein complex regulates activity of the traJ promoter of the Escherichia coli conjugative plasmid pRK100. J Bacteriol 185:1616–1623. http://dx.doi.org/10.1128/JB.185.5.1616-1623.2003. [PubMed]
269. Frost LS, Manchak J. 1998. F – phenocopies: characterization of expression of the F transfer region in stationary phase. Microbiology 144:2579–2587. http://dx.doi.org/10.1099/00221287-144-9-2579. [PubMed]
270. Will WR, Frost LS. 2006. Hfq is a regulator of F-plasmid TraJ and TraM synthesis in Escherichia coli. J Bacteriol 188:124–131. http://dx.doi.org/10.1128/JB.188.1.124-131.2006. [PubMed]
271. Lau-Wong IC, Locke T, Ellison MJ, Raivio TL, Frost LS. 2008. Activation of the Cpx regulon destabilizes the F plasmid transfer activator, TraJ, via the HslVU protease in Escherichia coli. Mol Microbiol 67:516–527. http://dx.doi.org/10.1111/j.1365-2958.2007.06055.x. [PubMed]
272. Zahrl D, Wagner A, Tscherner M, Koraimann G. 2007. GroEL plays a central role in stress-induced negative regulation of bacterial conjugation by promoting proteolytic degradation of the activator protein TraJ. J Bacteriol 189:5885–5894. http://dx.doi.org/10.1128/JB.00005-07. [PubMed]
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/content/journal/microbiolspec/10.1128/microbiolspec.MTBP-0015-2016
2018-01-11
2021-04-20

Abstract:

Conjugative plasmids are the main carriers of transmissible antibiotic resistance (AbR) genes. For that reason, strategies to control plasmid transmission have been proposed as potential solutions to prevent AbR dissemination. Natural mechanisms that bacteria employ as defense barriers against invading genomes, such as restriction-modification or CRISPR-Cas systems, could be exploited to control conjugation. Besides, conjugative plasmids themselves display mechanisms to minimize their associated burden or to compete with related or unrelated plasmids. Thus, FinOP systems, composed of FinO repressor protein and FinP antisense RNA, aid plasmids to regulate their own transfer; exclusion systems avoid conjugative transfer of related plasmids to the same recipient bacteria; and fertility inhibition systems block transmission of unrelated plasmids from the same donor cell. Artificial strategies have also been designed to control bacterial conjugation. For instance, intrabodies against R388 relaxase expressed in recipient cells inhibit plasmid R388 conjugative transfer; pIII protein of bacteriophage M13 inhibits plasmid F transmission by obstructing conjugative pili; and unsaturated fatty acids prevent transfer of clinically relevant plasmids in different hosts, promoting plasmid extinction in bacterial populations. Overall, a number of exogenous and endogenous factors have an effect on the sophisticated process of bacterial conjugation. This review puts them together in an effort to offer a wide picture and inform research to control plasmid transmission, focusing on Gram-negative bacteria.

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Natural and Artificial Strategies To Control the Conjugative Transmission of Plasmids
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Citation: Getino M, de la Cruz F. 2018. Natural and artificial strategies to control the conjugative transmission of plasmids. microbiolspec 6(1): doi:10.1128/microbiolspec.MTBP-0015-2016
/content/microbiolspec/10.1128/microbiolspec.MTBP-0015-2016.fig1
FIGURE 1
(1) The relaxase (R) cleaves plasmid DNA at the site and forms a covalent intermediate with the 5′ end of the . (2) The T4SS protein machinery recruits the relaxosome through interaction with the T4CP, while the donor DNA is replicated using the uncleaved DNA strand as a template. (3) The relaxase releases the T-strand by a second cleavage reaction at the site and acts as pilot protein for the ssDNA to be transferred through the T4SS, helped by the T4CP pumping activity. (4) In the recipient cell, the relaxase carries out the reverse nicking reaction to recircularize the T-strand. (5) The transferred ssDNA is replicated to generate a complete copy of the original plasmid.
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FIGURE 1

(1) The relaxase (R) cleaves plasmid DNA at the site and forms a covalent intermediate with the 5′ end of the . (2) The T4SS protein machinery recruits the relaxosome through interaction with the T4CP, while the donor DNA is replicated using the uncleaved DNA strand as a template. (3) The relaxase releases the T-strand by a second cleavage reaction at the site and acts as pilot protein for the ssDNA to be transferred through the T4SS, helped by the T4CP pumping activity. (4) In the recipient cell, the relaxase carries out the reverse nicking reaction to recircularize the T-strand. (5) The transferred ssDNA is replicated to generate a complete copy of the original plasmid.

Source: microbiolspec January 2018 vol. 6 no. 1 doi:10.1128/microbiolspec.MTBP-0015-2016
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FIGURE 2
Natural mechanisms include RM and CRISPR-Cas systems (encoded by the recipient chromosome), exclusion systems (used to prevent the entrance of related plasmids in the same recipient), and fertility inhibition systems (encoded by plasmids in donor bacteria). Artificial mechanisms interfere with key components of the conjugative process, such as the relaxase, the pilus, or conjugation-related ATPases.
microbiolspec/6/1/MTBP-0015-2016-fig2_thmb.gif
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FIGURE 2

Natural mechanisms include RM and CRISPR-Cas systems (encoded by the recipient chromosome), exclusion systems (used to prevent the entrance of related plasmids in the same recipient), and fertility inhibition systems (encoded by plasmids in donor bacteria). Artificial mechanisms interfere with key components of the conjugative process, such as the relaxase, the pilus, or conjugation-related ATPases.

Source: microbiolspec January 2018 vol. 6 no. 1 doi:10.1128/microbiolspec.MTBP-0015-2016
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FIGURE 3
Plasmid incompatibility groups are represented by colored circles. Continuous lines show fertility inhibition systems caused by genes in colored rectangles from plasmids in white boxes. Dashed lines show fertility inhibition systems caused by unidentified genes from plasmids in white boxes. See text for further details.
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FIGURE 3

Plasmid incompatibility groups are represented by colored circles. Continuous lines show fertility inhibition systems caused by genes in colored rectangles from plasmids in white boxes. Dashed lines show fertility inhibition systems caused by unidentified genes from plasmids in white boxes. See text for further details.

Source: microbiolspec January 2018 vol. 6 no. 1 doi:10.1128/microbiolspec.MTBP-0015-2016
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FIGURE 4
The tranquilizer chlorpromazine prevents plasmid conjugation and phage infection, possibly by modifying membrane topology. Male-specific bacteriophages bind the pilus tip through their pIII protein, blocking MPF and biofilm formation. Antibodies against conjugative pilus inhibit conjugation of specific plasmids. Zn in the mating medium blocks F pilus contact with Zn-containing receptor sites. Colloidal clay forms a coating on bacterial cells preventing liquid mating, phage infection, and predation. The opioid levallorphan inhibits MPF and adsorption of male-specific bacteriophages, probably by damaging pilus or bacterial membrane. Sodium periodate alters F pili, inhibiting donor fertility and bacteriophage infection. See the section on pilus blockers in the text for additional information.
microbiolspec/6/1/MTBP-0015-2016-fig4_thmb.gif
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FIGURE 4

The tranquilizer chlorpromazine prevents plasmid conjugation and phage infection, possibly by modifying membrane topology. Male-specific bacteriophages bind the pilus tip through their pIII protein, blocking MPF and biofilm formation. Antibodies against conjugative pilus inhibit conjugation of specific plasmids. Zn in the mating medium blocks F pilus contact with Zn-containing receptor sites. Colloidal clay forms a coating on bacterial cells preventing liquid mating, phage infection, and predation. The opioid levallorphan inhibits MPF and adsorption of male-specific bacteriophages, probably by damaging pilus or bacterial membrane. Sodium periodate alters F pili, inhibiting donor fertility and bacteriophage infection. See the section on pilus blockers in the text for additional information.

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Tables

Natural and Artificial Strategies To Control the Conjugative Transmission of Plasmids
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Citation: Getino M, de la Cruz F. 2018. Natural and artificial strategies to control the conjugative transmission of plasmids. microbiolspec 6(1): doi:10.1128/microbiolspec.MTBP-0015-2016
/content/microbiolspec/10.1128/microbiolspec.MTBP-0015-2016.T1
TABLE 1
Antirestriction strategies
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TABLE 1

Antirestriction strategies

Source: microbiolspec January 2018 vol. 6 no. 1 doi:10.1128/microbiolspec.MTBP-0015-2016
/content/microbiolspec/10.1128/microbiolspec.MTBP-0015-2016.T2
TABLE 2
Host-encoded factors involved in conjugative transfer of IncF plasmids
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TABLE 2

Host-encoded factors involved in conjugative transfer of IncF plasmids

Source: microbiolspec January 2018 vol. 6 no. 1 doi:10.1128/microbiolspec.MTBP-0015-2016

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