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.

Selection and Transmission of Antibiotic-Resistant Bacteria

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy this Microbiology Spectrum Article
Price Non-Member $15.00
  • Authors: Dan I. Andersson1, Diarmaid Hughes2
  • Editors: Fernando Baquero3, Emilio Bouza4, J.A. Gutiérrez-Fuentes5, Teresa M. Coque6
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; 2: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden; 3: Hospital Ramón y Cajal (IRYCIS), Madrid, Spain; 4: Hospital Ramón y Cajal (IRYCIS), Madrid, Spain; 5: Complutensis University, Madrid, Spain; 6: Hospital Ramón y Cajal (IRYCIS), Madrid, Spain
  • Source: microbiolspec July 2017 vol. 5 no. 4 doi:10.1128/microbiolspec.MTBP-0013-2016
  • Received 02 February 2017 Accepted 21 February 2017 Published 27 July 2017
  • Dan Andersson, Dan.Andersson@imbim.uu.se
image of Selection and Transmission of Antibiotic-Resistant Bacteria
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    Selection and Transmission of Antibiotic-Resistant Bacteria, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/5/4/MTBP-0013-2016-1.gif /docserver/preview/fulltext/microbiolspec/5/4/MTBP-0013-2016-2.gif
  • Abstract:

    Ever since antibiotics were introduced into human and veterinary medicine to treat and prevent bacterial infections there has been a steady selection and increase in the frequency of antibiotic resistant bacteria. To be able to reduce the rate of resistance evolution, we need to understand how various biotic and abiotic factors interact to drive the complex processes of resistance emergence and transmission. We describe several of the fundamental factors that underlay resistance evolution, including rates and niches of emergence and persistence of resistant bacteria, time- and space-gradients of various selective agents, and rates and routes of transmission of resistant bacteria between humans, animals and other environments. Furthermore, we discuss the options available to reduce the rate of resistance evolution and/ or transmission and their advantages and disadvantages.

  • Keywords: mutation rates; conjugation; successful clones; mobile genetic elements; selection; transmission; horizontal gene transfer; SOS; antibiotic resistance

  • Citation: Andersson D, Hughes D. 2017. Selection and Transmission of Antibiotic-Resistant Bacteria. Microbiol Spectrum 5(4):MTBP-0013-2016. doi:10.1128/microbiolspec.MTBP-0013-2016.

Key Concept Ranking

Single Nucleotide Polymorphism
0.4148285
Genetic Elements
0.4093135
0.4148285

References

1. Carlet J, Jarlier V, Harbarth S, Voss A, Goossens H, Pittet D, Participants of the 3rd World Healthcare-Associated Infections Forum. 2012. Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action. Antimicrob Resist Infect Control 1:11. http://dx.doi.org/10.1186/2047-2994-1-11.
2. Wittekamp BH, Bonten MJ. 2012. Antibiotic prophylaxis in the era of multidrug-resistant bacteria. Expert Opin Investig Drugs 21:767–772. http://dx.doi.org/10.1517/13543784.2012.681642.
3. Woodford N, Livermore DM. 2009. Infections caused by Gram-positive bacteria: a review of the global challenge. J Infect 59(Suppl 1):S4–S16. http://dx.doi.org/10.1016/S0163-4453(09)60003-7. [PubMed]
4. Procópio RE, Silva IR, Martins MK, Azevedo JL, Araújo JM. 2012. Antibiotics produced by Streptomyces. Braz J Infect Dis 16:466–471. http://dx.doi.org/10.1016/j.bjid.2012.08.014.
5. Hasani A, Kariminik A, Issazadeh K. 2014. Streptomycetes: characteristics and their antimicrobial activities. Int J Adv Biol Biomed Res 2:63–75.
6. Hall BG, Barlow M. 2004. Evolution of the serine β-lactamases: past, present and future. Drug Resist Updat 7:111–123. http://dx.doi.org/10.1016/j.drup.2004.02.003.
7. Bhullar K, Waglechner N, Pawlowski A, Koteva K, Banks ED, Johnston MD, Barton HA, Wright GD. 2012. Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS One 7:e34953. http://dx.doi.org/10.1371/journal.pone.0034953. [PubMed]
8. D’Costa VM, King CE, Kalan L, Morar M, Sung WW, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD. 2011. Antibiotic resistance is ancient. Nature 477:457–461. http://dx.doi.org/10.1038/nature10388.
9. Petrova M, Gorlenko Z, Mindlin S. 2011. Tn5045, a novel integron-containing antibiotic and chromate resistance transposon isolated from a permafrost bacterium. Res Microbiol 162:337–345. http://dx.doi.org/10.1016/j.resmic.2011.01.003. [PubMed]
10. Waksman SA, Woodruff HB. 1940. The soil as a source of microorganisms antagonistic to disease-producing bacteria. J Bacteriol 40:581–600. [PubMed]
11. Martinez JL, Fajardo A, Garmendia L, Hernandez A, Linares JF, Martínez-Solano L, Sánchez MB. 2009. A global view of antibiotic resistance. FEMS Microbiol Rev 33:44–65. http://dx.doi.org/10.1111/j.1574-6976.2008.00142.x. [PubMed]
12. Abrudan MI, Smakman F, Grimbergen AJ, Westhoff S, Miller EL, van Wezel GP, Rozen DE. 2015. Socially mediated induction and suppression of antibiosis during bacterial coexistence. Proc Natl Acad Sci U S A 112:11054–11059. http://dx.doi.org/10.1073/pnas.1504076112.
13. Ruiz J, Pons MJ, Gomes C. 2012. Transferable mechanisms of quinolone resistance. Int J Antimicrob Agents 40:196–203. http://dx.doi.org/10.1016/j.ijantimicag.2012.02.011.
14. Robicsek A, Jacoby GA, Hooper DC. 2006. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 6:629–640. http://dx.doi.org/10.1016/S1473-3099(06)70599-0.
15. Robicsek A, Strahilevitz J, Jacoby GA, Macielag M, Abbanat D, Park CH, Bush K, Hooper DC. 2006. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat Med 12:83–88. http://dx.doi.org/10.1038/nm1347.
16. Favrot L, Blanchard JS, Vergnolle O. 2016. Bacterial GCN5-related N-acetyltransferases: from resistance to regulation. Biochemistry 55:989–1002. http://dx.doi.org/10.1021/acs.biochem.5b01269.
17. Kelly JA, Dideberg O, Charlier P, Wery JP, Libert M, Moews PC, Knox JR, Duez C, Fraipont C, Joris B, Dusart J, Frere JM, Ghuysen JM. 1986. On the origin of bacterial resistance to penicillin: comparison of a beta-lactamase and a penicillin target. Science 231:1429–1431. http://dx.doi.org/10.1126/science.3082007.
18. Massova I, Mobashery S. 1998. Kinship and diversification of bacterial penicillin-binding proteins and β-lactamases. Antimicrob Agents Chemother 42:1–17. [PubMed]
19. Chesnel L, Zapun A, Mouz N, Dideberg O, Vernet T. 2002. Increase of the deacylation rate of PBP2x from Streptococcus pneumoniae by single point mutations mimicking the class A β-lactamases. Eur J Biochem 269:1678–1683. http://dx.doi.org/10.1046/j.1432-1327.2002.02815.x.
20. Peimbert M, Segovia L. 2003. Evolutionary engineering of a β-lactamase activity on a d-Ala d-Ala transpeptidase fold. Protein Eng 16:27–35. http://dx.doi.org/10.1093/proeng/gzg008.
21. Sun S, Selmer M, Andersson DI. 2014. Resistance to β-lactam antibiotics conferred by point mutations in penicillin-binding proteins PBP3, PBP4 and PBP6 in Salmonella enterica. PLoS One 9:e97202. http://dx.doi.org/10.1371/journal.pone.0097202.
22. Yang W, Moore IF, Koteva KP, Bareich DC, Hughes DW, Wright GD. 2004. TetX is a flavin-dependent monooxygenase conferring resistance to tetracycline antibiotics. J Biol Chem 279:52346–52352. http://dx.doi.org/10.1074/jbc.M409573200.
23. Linkevicius M, Sandegren L, Andersson DI. 2015. Potential of tetracycline resistance proteins to evolve tigecycline resistance. Antimicrob Agents Chemother 60:789–796. http://dx.doi.org/10.1128/AAC.02465-15. [PubMed]
24. Soucy SM, Huang J, Gogarten JP. 2015. Horizontal gene transfer: building the web of life. Nat Rev Genet 16:472–482. http://dx.doi.org/10.1038/nrg3962.
25. Wright GD. 2010. Antibiotic resistance in the environment: a link to the clinic? Curr Opin Microbiol 13:589–594. http://dx.doi.org/10.1016/j.mib.2010.08.005. [PubMed]
26. Perry JA, Westman EL, Wright GD. 2014. The antibiotic resistome: what’s new? Curr Opin Microbiol 21:45–50. http://dx.doi.org/10.1016/j.mib.2014.09.002.
27. Poirel L, Kämpfer P, Nordmann P. 2002. Chromosome-encoded Ambler class A β-lactamase of Kluyvera georgiana, a probable progenitor of a subgroup of CTX-M extended-spectrum β-lactamases. Antimicrob Agents Chemother 46:4038–4040. http://dx.doi.org/10.1128/AAC.46.12.4038-4040.2002.
28. Humeniuk C, Arlet G, Gautier V, Grimont P, Labia R, Philippon A. 2002. β-Lactamases of Kluyvera ascorbata, probable progenitors of some plasmid-encoded CTX-M types. Antimicrob Agents Chemother 46:3045–3049. http://dx.doi.org/10.1128/AAC.46.9.3045-3049.2002.
29. Decousser JW, Poirel L, Nordmann P. 2001. Characterization of a chromosomally encoded extended-spectrum class A β-lactamase from Kluyvera cryocrescens. Antimicrob Agents Chemother 45:3595–3598. http://dx.doi.org/10.1128/AAC.45.12.3595-3598.2001.
30. Poirel L, Lartigue MF, Decousser JW, Nordmann P. 2005. ISEcp1B-mediated transposition of blaCTX-M in Escherichia coli. Antimicrob Agents Chemother 49:447–450. http://dx.doi.org/10.1128/AAC.49.1.447-450.2005. [PubMed]
31. Poirel L, Rodriguez-Martinez JM, Mammeri H, Liard A, Nordmann P. 2005. Origin of plasmid-mediated quinolone resistance determinant QnrA. Antimicrob Agents Chemother 49:3523–3525. http://dx.doi.org/10.1128/AAC.49.8.3523-3525.2005.
32. Poirel L, Héritier C, Nordmann P. 2004. Chromosome-encoded Ambler class D β-lactamase of Shewanella oneidensis as a progenitor of carbapenem-hydrolyzing oxacillinase. Antimicrob Agents Chemother 48:348–351. http://dx.doi.org/10.1128/AAC.48.1.348-351.2004.
33. Guiney DG, Jr, Hasegawa P, Davis CE. 1984. Expression in Escherichia coli of cryptic tetracycline resistance genes from bacteroides R plasmids. Plasmid 11:248–252. http://dx.doi.org/10.1016/0147-619X(84)90031-3.
34. Park BH, Levy SB. 1988. The cryptic tetracycline resistance determinant on Tn4400 mediates tetracycline degradation as well as tetracycline efflux. Antimicrob Agents Chemother 32:1797–1800. http://dx.doi.org/10.1128/AAC.32.12.1797.
35. Speer BS, Salyers AA. 1988. Characterization of a novel tetracycline resistance that functions only in aerobically grown Escherichia coli.J Bacteriol 170:1423–1429. http://dx.doi.org/10.1128/jb.170.4.1423-1429.1988. [PubMed]
36. Bartha NA, Sóki J, Urbán E, Nagy E. 2011. Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations. Int J Antimicrob Agents 38:522–525. http://dx.doi.org/10.1016/j.ijantimicag.2011.07.010.
37. de Vries LE, Vallès Y, Agersø Y, Vaishampayan PA, García-Montaner A, Kuehl JV, Christensen H, Barlow M, Francino MP. 2011. The gut as reservoir of antibiotic resistance: microbial diversity of tetracycline resistance in mother and infant. PLoS One 6:e21644. http://dx.doi.org/10.1371/journal.pone.0021644.
38. Ghosh S, Sadowsky MJ, Roberts MC, Gralnick JA, LaPara TM. 2009. Sphingobacterium sp. strain PM2-P1-29 harbours a functional tet(X) gene encoding for the degradation of tetracycline. J Appl Microbiol 106:1336–1342. http://dx.doi.org/10.1111/j.1365-2672.2008.04101.x.
39. Heuer H, Kopmann C, Binh CTT, Top EM, Smalla K. 2009. Spreading antibiotic resistance through spread manure: characteristics of a novel plasmid type with low %G+C content. Environ Microbiol 11:937–949. http://dx.doi.org/10.1111/j.1462-2920.2008.01819.x.
40. Zhang XX, Zhang T. 2011. Occurrence, abundance, and diversity of tetracycline resistance genes in 15 sewage treatment plants across China and other global locations. Environ Sci Technol 45:2598–2604. http://dx.doi.org/10.1021/es103672x.
41. Leski TA, Bangura U, Jimmy DH, Ansumana R, Lizewski SE, Stenger DA, Taitt CR, Vora GJ. 2013. Multidrug-resistant tet(X)-containing hospital isolates in Sierra Leone. Int J Antimicrob Agents 42:83–86. http://dx.doi.org/10.1016/j.ijantimicag.2013.04.014.
42. Knapp CW, Dolfing J, Ehlert PAI, Graham DW. 2010. Evidence of increasing antibiotic resistance gene abundances in archived soils since 1940. Environ Sci Technol 44:580–587. http://dx.doi.org/10.1021/es901221x.
43. Hughes VM, Datta N. 1983. Conjugative plasmids in bacteria of the ‘pre-antibiotic’ era. Nature 302:725–726. http://dx.doi.org/10.1038/302725a0.
44. Bellanger X, Guilloteau H, Bonot S, Merlin C. 2014. Demonstrating plasmid-based horizontal gene transfer in complex environmental matrices: a practical approach for a critical review. Sci Total Environ 493:872–882. http://dx.doi.org/10.1016/j.scitotenv.2014.06.070.
45. Michael I, Rizzo L, McArdell CS, Manaia CM, Merlin C, Schwartz T, Dagot C, Fatta-Kassinos D. 2013. Urban wastewater treatment plants as hotspots for the release of antibiotics in the environment: a review. Water Res 47:957–995. http://dx.doi.org/10.1016/j.watres.2012.11.027.
46. Marti E, Variatza E, Balcazar JL. 2014. The role of aquatic ecosystems as reservoirs of antibiotic resistance. Trends Microbiol 22:36–41. http://dx.doi.org/10.1016/j.tim.2013.11.001.
47. Bouki C, Venieri D, Diamadopoulos E. 2013. Detection and fate of antibiotic resistant bacteria in wastewater treatment plants: a review. Ecotoxicol Environ Saf 91:1–9. http://dx.doi.org/10.1016/j.ecoenv.2013.01.016.
48. Zhang XX, Zhang T, Fang HH. 2009. Antibiotic resistance genes in water environment. Appl Microbiol Biotechnol 82:397–414. http://dx.doi.org/10.1007/s00253-008-1829-z.
49. Pei J, Yao H, Wang H, Ren J, Yu X. 2016. Comparison of ozone and thermal hydrolysis combined with anaerobic digestion for municipal and pharmaceutical waste sludge with tetracycline resistance genes. Water Res 99:122–128. http://dx.doi.org/10.1016/j.watres.2016.04.058.
50. Oh J, Salcedo DE, Medriano CA, Kim S. 2014. Comparison of different disinfection processes in the effective removal of antibiotic-resistant bacteria and genes. J Environ Sci (China) 26:1238–1242. http://dx.doi.org/10.1016/S1001-0742(13)60594-X.
51. Kimura M, Ohta T. 1969. The average number of generations until fixation of a mutant gene in a finite population. Genetics 61:763–771. [PubMed]
52. Charlesworth B. 2009. Fundamental concepts in genetics: effective population size and patterns of molecular evolution and variation. Nat Rev Genet 10:195–205. http://dx.doi.org/10.1038/nrg2526. [PubMed]
53. Berg OG. 1996. Selection intensity for codon bias and the effective population size of Escherichia coli. Genetics 142:1379–1382. [PubMed]
54. Andersson DI, Hughes D. 2011. Persistence of antibiotic resistance in bacterial populations. FEMS Microbiol Rev 35:901–911. http://dx.doi.org/10.1111/j.1574-6976.2011.00289.x.
55. van de Sande-Bruinsma N, Grundmann H, Verloo D, Tiemersma E, Monen J, Goossens H, Ferech M, European Antimicrobial Resistance Surveillance System Group, European Surveillance of Antimicrobial Consumption Project Group. 2008. Antimicrobial drug use and resistance in Europe. Emerg Infect Dis 14:1722–1730. http://dx.doi.org/10.3201/eid1411.070467.
56. Bergman M, Nyberg ST, Huovinen P, Paakkari P, Hakanen AJ, Finnish Study Group for Antimicrobial Resistance. 2009. Association between antimicrobial consumption and resistance in Escherichia coli. Antimicrob Agents Chemother 53:912–917. http://dx.doi.org/10.1128/AAC.00856-08.
57. Goossens H. 2009. Antibiotic consumption and link to resistance. Clin Microbiol Infect 15(Suppl 3):12–15. http://dx.doi.org/10.1111/j.1469-0691.2009.02725.x.
58. Drlica K, Zhao X. 2007. Mutant selection window hypothesis updated. Clin Infect Dis 44:681–688. http://dx.doi.org/10.1086/511642. [PubMed]
59. Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D, Andersson DI. 2011. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog 7:e1002158. http://dx.doi.org/10.1371/journal.ppat.1002158.
60. Liu A, Fong A, Becket E, Yuan J, Tamae C, Medrano L, Maiz M, Wahba C, Lee C, Lee K, Tran KP, Yang H, Hoffman RM, Salih A, Miller JH. 2011. Selective advantage of resistant strains at trace levels of antibiotics: a simple and ultrasensitive color test for detection of antibiotics and genotoxic agents. Antimicrob Agents Chemother 55:1204–1210. http://dx.doi.org/10.1128/AAC.01182-10.
61. Gullberg E, Albrecht LM, Karlsson C, Sandegren L, Andersson DI. 2014. Selection of a multidrug resistance plasmid by sublethal levels of antibiotics and heavy metals. mBio 5:e01918-e14. http://dx.doi.org/10.1128/mBio.01918-14.
62. Baquero F, Coque TM. 2014. Widening the spaces of selection: evolution along sublethal antimicrobial gradients. mBio 5:e02270. http://dx.doi.org/10.1128/mBio.02270-14. [PubMed]
63. Andersson DI, Hughes D. 2014. Microbiological effects of sublethal levels of antibiotics. Nat Rev Microbiol 12:465–478. http://dx.doi.org/10.1038/nrmicro3270.
64. Scientific Committee on Emerging and Newly Identified Health Risks (SCENHIR). 2009. Assessment of the Antibiotic Resistance Effects of Biocides. European Union, Brussels, Belgium. http://ec.europa.eu/health/ph_risk/committees/04_scenihr/docs/scenihr_o_021.pdf. Accessed 19 July 2017.
65. European Chemicals Agency (ECHA). Biocidal Products Regulation. ECHA, Helsinki, Finland. https://echa.europa.eu/regulations/biocidal-products-regulation. Accessed 19 July 2017.
66. Webber MA, Whitehead RN, Mount M, Loman NJ, Pallen MJ, Piddock LJ. 2015. Parallel evolutionary pathways to antibiotic resistance selected by biocide exposure. J Antimicrob Chemother 70:2241–2248. http://dx.doi.org/10.1093/jac/dkv109.
67. Webber MA, Randall LP, Cooles S, Woodward MJ, Piddock LJ. 2008. Triclosan resistance in Salmonella enterica serovar Typhimurium. J Antimicrob Chemother 62:83–91. http://dx.doi.org/10.1093/jac/dkn137.
68. Sivaraman S, Zwahlen J, Bell AF, Hedstrom L, Tonge PJ. 2003. Structure-activity studies of the inhibition of FabI, the enoyl reductase from Escherichia coli, by triclosan: kinetic analysis of mutant FabIs. Biochemistry 42:4406–4413. http://dx.doi.org/10.1021/bi0300229.
69. Pal C, Bengtsson-Palme J, Kristiansson E, Larsson DG. 2015. Co-occurrence of resistance genes to antibiotics, biocides and metals reveals novel insights into their co-selection potential. BMC Genomics 16:964. http://dx.doi.org/10.1186/s12864-015-2153-5.
70. U.S. Department of Agriculture (USDA). Maximum Residue Limits (MRL) Database. USDA, Washington, DC. http://www.fas.usda.gov/maximum-residue-limits-mrl-database. Accessed 19 July 2017.
71. Mathers AJ, Peirano G, Pitout JD. 2015. The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin Microbiol Rev 28:565–591. http://dx.doi.org/10.1128/CMR.00116-14.
72. McNally A, Oren Y, Kelly D, Pascoe B, Dunn S, Sreecharan T, Vehkala M, Välimäki N, Prentice MB, Ashour A, Avram O, Pupko T, Dobrindt U, Literak I, Guenther S, Schaufler K, Wieler LH, Zhiyong Z, Sheppard SK, McInerney JO, Corander J. 2016. Combined analysis of variation in core, accessory and regulatory genome regions provides a super-resolution view into the evolution of bacterial populations. PLoS Genet 12:e1006280. http://dx.doi.org/10.1371/journal.pgen.1006280.
73. Enne VI, Bennett PM, Livermore DM, Hall LM. 2004. Enhancement of host fitness by the sul2-coding plasmid p9123 in the absence of selective pressure. J Antimicrob Chemother 53:958–963. http://dx.doi.org/10.1093/jac/dkh217.
74. Dionisio F, Conceição IC, Marques AC, Fernandes L, Gordo I. 2005. The evolution of a conjugative plasmid and its ability to increase bacterial fitness. Biol Lett 1:250–252. http://dx.doi.org/10.1098/rsbl.2004.0275. [PubMed]
75. Yates CM, Shaw DJ, Roe AJ, Woolhouse ME, Amyes SG. 2006. Enhancement of bacterial competitive fitness by apramycin resistance plasmids from non-pathogenic Escherichia coli. Biol Lett 2:463–465. http://dx.doi.org/10.1098/rsbl.2006.0478.
76. Bouma JE, Lenski RE. 1988. Evolution of a bacteria/plasmid association. Nature 335:351–352. http://dx.doi.org/10.1038/335351a0.
77. Starikova I, Al-Haroni M, Werner G, Roberts AP, Sørum V, Nielsen KM, Johnsen PJ. 2013. Fitness costs of various mobile genetic elements in Enterococcus faecium and Enterococcus faecalis. J Antimicrob Chemother 68:2755–2765. http://dx.doi.org/10.1093/jac/dkt270.
78. Andersson DI, Hughes D. 2010. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol 8:260–271. http://dx.doi.org/10.1038/nrmicro2319.
79. Hughes D, Andersson DI. 2015. Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms. Nat Rev Genet 16:459–471. http://dx.doi.org/10.1038/nrg3922.
80. Cirz RT, Romesberg FE. 2006. Induction and inhibition of ciprofloxacin resistance-conferring mutations in hypermutator bacteria. Antimicrob Agents Chemother 50:220–225. http://dx.doi.org/10.1128/AAC.50.1.220-225.2006.
81. Alam MK, Alhhazmi A, DeCoteau JF, Luo Y, Geyer CR. 2016. RecA inhibitors potentiate antibiotic activity and block evolution of antibiotic resistance. Cell Chem Biol 23:381–391. http://dx.doi.org/10.1016/j.chembiol.2016.02.010. [PubMed]
82. Culyba MJ, Mo CY, Kohli RM. 2015. Targets for combating the evolution of acquired antibiotic resistance. Biochemistry 54:3573–3582. http://dx.doi.org/10.1021/acs.biochem.5b00109.
83. 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.
84. Kim S, Lieberman TD, Kishony R. 2014. Alternating antibiotic treatments constrain evolutionary paths to multidrug resistance. Proc Natl Acad Sci U S A 111:14494–14499. http://dx.doi.org/10.1073/pnas.1409800111. [PubMed]
85. Imamovic L, Sommer MO. 2013. Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development. Sci Transl Med 5:204ra132. http://dx.doi.org/10.1126/scitranslmed.3006609.
86. Lázár V, Nagy I, Spohn R, Csörgő B, Györkei Á, Nyerges Á, Horváth B, Vörös A, Busa-Fekete R, Hrtyan M, Bogos B, Méhi O, Fekete G, Szappanos B, Kégl B, Papp B, Pál C. 2014. Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network. Nat Commun 5:4352. http://dx.doi.org/10.1038/ncomms5352.
87. Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. 2015. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol 13:42–51. http://dx.doi.org/10.1038/nrmicro3380.
88. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J. 2016. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16:161–168. http://dx.doi.org/10.1016/S1473-3099(15)00424-7.
89. Hakenbeck R, Brückner R, Denapaite D, Maurer P. 2012. Molecular mechanisms of β-lactam resistance in Streptococcus pneumoniae. Future Microbiol 7:395–410. http://dx.doi.org/10.2217/fmb.12.2.
90. Tapsall JW. 2009. Neisseria gonorrhoeae and emerging resistance to extended spectrum cephalosporins. Curr Opin Infect Dis 22:87–91. http://dx.doi.org/10.1097/QCO.0b013e328320a836.
91. Finlay BB, Falkow S. 1997. Common themes in microbial pathogenicity revisited. Microbiol Mol Biol Rev 61:136–169. [PubMed]
92. von Wintersdorff CJ, Penders J, van Niekerk JM, Mills ND, Majumder S, van Alphen LB, Savelkoul PH, Wolffs PF. 2016. Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer. Front Microbiol 7:173. http://dx.doi.org/10.3389/fmicb.2016.00173.
93. Butala M, Zgur-Bertok D, Busby SJ. 2009. The bacterial LexA transcriptional repressor. Cell Mol Life Sci 66:82–93. http://dx.doi.org/10.1007/s00018-008-8378-6.
94. Drlica K, Zhao X. 1997. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 61:377–392. [PubMed]
95. Maiques E, Ubeda C, Campoy S, Salvador N, Lasa I, Novick RP, Barbé J, Penadés JR. 2006. β-Lactam antibiotics induce the SOS response and horizontal transfer of virulence factors in Staphylococcus aureus. J Bacteriol 188:2726–2729. http://dx.doi.org/10.1128/JB.188.7.2726-2729.2006.
96. Lewin CS, Amyes SG. 1991. The role of the SOS response in bacteria exposed to zidovudine or trimethoprim. J Med Microbiol 34:329–332. http://dx.doi.org/10.1099/00222615-34-6-329.
97. Baharoglu Z, Mazel D. 2011. Vibrio cholerae triggers SOS and mutagenesis in response to a wide range of antibiotics: a route towards multiresistance. Antimicrob Agents Chemother 55:2438–2441. http://dx.doi.org/10.1128/AAC.01549-10.
98. 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.
99. Ubeda C, Maiques E, Knecht E, Lasa I, Novick RP, Penadés JR. 2005. Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci. Mol Microbiol 56:836–844. http://dx.doi.org/10.1111/j.1365-2958.2005.04584.x.
100. Chen J, Novick RP. 2009. Phage-mediated intergeneric transfer of toxin genes. Science 323:139–141. http://dx.doi.org/10.1126/science.1164783. [PubMed]
101. Zhang X, McDaniel AD, Wolf LE, Keusch GT, Waldor MK, Acheson DW. 2000. Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice. J Infect Dis 181:664–670. http://dx.doi.org/10.1086/315239.
102. Bearson BL, Brunelle BW. 2015. Fluoroquinolone induction of phage-mediated gene transfer in multidrug-resistant Salmonella. Int J Antimicrob Agents 46:201–204. http://dx.doi.org/10.1016/j.ijantimicag.2015.04.008.
103. Torres OR, Korman RZ, Zahler SA, Dunny GM. 1991. The conjugative transposon Tn925: 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.
104. 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.
105. 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]
106. Prudhomme M, Attaiech L, Sanchez G, Martin B, Claverys JP. 2006. Antibiotic stress induces genetic transformability in the human pathogen Streptococcus pneumoniae. Science 313:89–92. http://dx.doi.org/10.1126/science.1127912.
107. López E, Elez M, Matic I, Blázquez J. 2007. Antibiotic-mediated recombination: ciprofloxacin stimulates SOS-independent recombination of divergent sequences in Escherichia coli. Mol Microbiol 64:83–93. http://dx.doi.org/10.1111/j.1365-2958.2007.05642.x. [PubMed]
108. Guerin E, Cambray G, Sanchez-Alberola N, Campoy S, Erill I, Da Re S, Gonzalez-Zorn B, Barbé J, Ploy MC, Mazel D. 2009. The SOS response controls integron recombination. Science 324:1034. http://dx.doi.org/10.1126/science.1172914.
109. Hocquet D, Llanes C, Thouverez M, Kulasekara HD, Bertrand X, Plésiat P, Mazel D, Miller SI. 2012. Evidence for induction of integron-based antibiotic resistance by the SOS response in a clinical setting. PLoS Pathog 8:e1002778. http://dx.doi.org/10.1371/journal.ppat.1002778. [PubMed]
110. 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.
111. 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]
112. 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.
113. 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.
114. 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.
115. Machado AM, Sommer MO. 2014. Human intestinal cells modulate conjugational transfer of multidrug resistance plasmids between clinical Escherichia coli isolates. PLoS One 9:e100739. http://dx.doi.org/10.1371/journal.pone.0100739.
116. Cirz RT, Chin JK, Andes DR, de Crécy-Lagard V, Craig WA, Romesberg FE. 2005. Inhibition of mutation and combating the evolution of antibiotic resistance. PLoS Biol 3:e176. http://dx.doi.org/10.1371/journal.pbio.0030176.
117. Mo CY, Manning SA, Roggiani M, Culyba MJ, Samuels AN, Sniegowski PD, Goulian M, Kohli RM. 2016. Systematically altering bacterial SOS activity under stress reveals therapeutic strategies for potentiating antibiotics. mSphere 1:e00163-16. http://dx.doi.org/10.1128/mSphere.00163-16.
118. Wigle TJ, Sexton JZ, Gromova AV, Hadimani MB, Hughes MA, Smith GR, Yeh LA, Singleton SF. 2009. Inhibitors of RecA activity discovered by high-throughput screening: cell-permeable small molecules attenuate the SOS response in Escherichia coli. J Biomol Screen 14:1092–1101. http://dx.doi.org/10.1177/1087057109342126. [PubMed]
119. Peng Q, Zhou S, Yao F, Hou B, Huang Y, Hua D, Zheng Y, Qian Y. 2011. Baicalein suppresses the SOS response system of Staphylococcus aureus induced by ciprofloxacin. Cell Physiol Biochem 28:1045–1050. http://dx.doi.org/10.1159/000335791.
120. Nautiyal A, Patil KN, Muniyappa K. 2014. Suramin is a potent and selective inhibitor of Mycobacterium tuberculosis RecA protein and the SOS response: RecA as a potential target for antibacterial drug discovery. J Antimicrob Chemother 69:1834–1843. http://dx.doi.org/10.1093/jac/dku080.
121. Holmes AH, Moore LS, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, Guerin PJ, Piddock LJ. 2016. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 387:176–187. http://dx.doi.org/10.1016/S0140-6736(15)00473-0.
122. Yates TA, Khan PY, Knight GM, Taylor JG, McHugh TD, Lipman M, White RG, Cohen T, Cobelens FG, Wood R, Moore DA, Abubakar I. 2016. The transmission of Mycobacterium tuberculosis in high burden settings. Lancet Infect Dis 16:227–238. http://dx.doi.org/10.1016/S1473-3099(15)00499-5.
123. Aarestrup FM. 2015. The livestock reservoir for antimicrobial resistance: a personal view on changing patterns of risks, effects of interventions and the way forward. Philos Trans R Soc Lond B Biol Sci 370:20140085. http://dx.doi.org/10.1098/rstb.2014.0085.
124. Huijbers PM, Blaak H, de Jong MC, Graat EA, Vandenbroucke-Grauls CM, de Roda Husman AM. 2015. Role of the environment in the transmission of antimicrobial resistance to humans: a review. Environ Sci Technol 49:11993–12004. http://dx.doi.org/10.1021/acs.est.5b02566.
125. Arnold KE, Williams NJ, Bennett M. 2016. ‘Disperse abroad in the land’: the role of wildlife in the dissemination of antimicrobial resistance. Biol Lett 12:12. http://dx.doi.org/10.1098/rsbl.2016.0137.
126. Croxen MA, Finlay BB. 2010. Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Microbiol 8:26–38. http://dx.doi.org/10.1038/nrmicro2265. [PubMed]
127. Nicolas-Chanoine MH, Bertrand X, Madec JY. 2014. Escherichia coli ST131, an intriguing clonal group. Clin Microbiol Rev 27:543–574. http://dx.doi.org/10.1128/CMR.00125-13.
128. Nicolas-Chanoine MH, Blanco J, Leflon-Guibout V, Demarty R, Alonso MP, Caniça MM, Park YJ, Lavigne JP, Pitout J, Johnson JR. 2008. Intercontinental emergence of Escherichia coli clone O25:H4-ST131 producing CTX-M-15. J Antimicrob Chemother 61:273–281. http://dx.doi.org/10.1093/jac/dkm464.
129. Coque TM, Novais A, Carattoli A, Poirel L, Pitout J, Peixe L, Baquero F, Cantón R, Nordmann P. 2008. Dissemination of clonally related Escherichia coli strains expressing extended-spectrum β-lactamase CTX-M-15. Emerg Infect Dis 14:195–200. http://dx.doi.org/10.3201/eid1402.070350.
130. Johnson JR, Tchesnokova V, Johnston B, Clabots C, Roberts PL, Billig M, Riddell K, Rogers P, Qin X, Butler-Wu S, Price LB, Aziz M, Nicolas-Chanoine MH, Debroy C, Robicsek A, Hansen G, Urban C, Platell J, Trott DJ, Zhanel G, Weissman SJ, Cookson BT, Fang FC, Limaye AP, Scholes D, Chattopadhyay S, Hooper DC, Sokurenko EV. 2013. Abrupt emergence of a single dominant multidrug-resistant strain of Escherichia coli. J Infect Dis 207:919–928. http://dx.doi.org/10.1093/infdis/jis933.
131. Price LB, Johnson JR, Aziz M, Clabots C, Johnston B, Tchesnokova V, Nordstrom L, Billig M, Chattopadhyay S, Stegger M, Andersen PS, Pearson T, Riddell K, Rogers P, Scholes D, Kahl B, Keim P, Sokurenko EV. 2013. The epidemic of extended-spectrum-β-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. mBio 4:e00377-e13. http://dx.doi.org/10.1128/mBio.00377-13.
132. Woodford N, Carattoli A, Karisik E, Underwood A, Ellington MJ, Livermore DM. 2009. Complete nucleotide sequences of plasmids pEK204, pEK499, and pEK516, encoding CTX-M enzymes in three major Escherichia coli lineages from the United Kingdom, all belonging to the international O25:H4-ST131 clone. Antimicrob Agents Chemother 53:4472–4482. http://dx.doi.org/10.1128/AAC.00688-09.
133. Naseer U, Haldorsen B, Tofteland S, Hegstad K, Scheutz F, Simonsen GS, Sundsfjord A, Norwegian ESBL Study Group. 2009. Molecular characterization of CTX-M-15-producing clinical isolates of Escherichia coli reveals the spread of multidrug-resistant ST131 (O25:H4) and ST964 (O102:H6) strains in Norway. APMIS 117:526–536. http://dx.doi.org/10.1111/j.1600-0463.2009.02465.x.
134. Novais Â, Viana D, Baquero F, Martínez-Botas J, Cantón R, Coque TM. 2012. Contribution of IncFII and broad-host IncA/C and IncN plasmids to the local expansion and diversification of phylogroup B2 Escherichia coli ST131 clones carrying blaCTX-M-15 and qnrS1 genes. Antimicrob Agents Chemother 56:2763–2766. http://dx.doi.org/10.1128/AAC.06001-11.
135. Partridge SR, Ellem JA, Tetu SG, Zong Z, Paulsen IT, Iredell JR. 2011. Complete sequence of pJIE143, a pir-type plasmid carrying ISEcp1-blaCTX-M-15 from an Escherichia coli ST131 isolate. Antimicrob Agents Chemother 55:5933–5935. http://dx.doi.org/10.1128/AAC.00639-11. [PubMed]
136. Bonnin RA, Poirel L, Carattoli A, Nordmann P. 2012. Characterization of an IncFII plasmid encoding NDM-1 from Escherichia coli ST131. PLoS One 7:e34752. http://dx.doi.org/10.1371/journal.pone.0034752.
137. Mathers AJ, Peirano G, Pitout JD. 2015. Escherichia coli ST131: the quintessential example of an international multiresistant high-risk clone. Adv Appl Microbiol 90:109–154. http://dx.doi.org/10.1016/bs.aambs.2014.09.002. [PubMed]
138. Banerjee R, Johnson JR. 2014. A new clone sweeps clean: the enigmatic emergence of Escherichia coli sequence type 131. Antimicrob Agents Chemother 58:4997–5004. http://dx.doi.org/10.1128/AAC.02824-14.
139. Hilty M, Betsch BY, Bögli-Stuber K, Heiniger N, Stadler M, Küffer M, Kronenberg A, Rohrer C, Aebi S, Endimiani A, Droz S, Mühlemann K. 2012. Transmission dynamics of extended-spectrum β-lactamase-producing Enterobacteriaceae in the tertiary care hospital and the household setting. Clin Infect Dis 55:967–975. http://dx.doi.org/10.1093/cid/cis581.
140. Johnson JR, Miller S, Johnston B, Clabots C, Debroy C. 2009. Sharing of Escherichia coli sequence type ST131 and other multidrug-resistant and urovirulent E. coli strains among dogs and cats within a household. J Clin Microbiol 47:3721–3725. http://dx.doi.org/10.1128/JCM.01581-09.
141. Banerjee R, Robicsek A, Kuskowski MA, Porter S, Johnston BD, Sokurenko E, Tchesnokova V, Price LB, Johnson JR. 2013. Molecular epidemiology of Escherichia coli sequence type 131 and its H30 and H30-Rx subclones among extended-spectrum-β-lactamase-positive and -negative E. coli clinical isolates from the Chicago region, 2007 to 2010. Antimicrob Agents Chemother 57:6385–6388. http://dx.doi.org/10.1128/AAC.01604-13.
142. Johnson TJ, Hargreaves M, Shaw K, Snippes P, Lynfield R, Aziz M, Price LB. 2015. Complete genome sequence of a carbapenem-resistant extraintestinal pathogenic Escherichia coli strain belonging to the sequence type 131 H30R subclade. Genome Announc 3:e00272-15. http://dx.doi.org/10.1128/genomeA.00272-15.
143. Accogli M, Giani T, Monaco M, Giufrè M, García-Fernández A, Conte V, D’Ancona F, Pantosti A, Rossolini GM, Cerquetti M. 2014. Emergence of Escherichia coli ST131 sub-clone H30 producing VIM-1 and KPC-3 carbapenemases, Italy. J Antimicrob Chemother 69:2293–2296. http://dx.doi.org/10.1093/jac/dku132.
144. Cai JC, Zhang R, Hu YY, Zhou HW, Chen GX. 2014. Emergence of Escherichia coli sequence type 131 isolates producing KPC-2 carbapenemase in China. Antimicrob Agents Chemother 58:1146–1152. http://dx.doi.org/10.1128/AAC.00912-13.
145. Naas T, Cuzon G, Gaillot O, Courcol R, Nordmann P. 2011. When carbapenem-hydrolyzing β-lactamase Kpc meets Escherichia coli ST131 in France. Antimicrob Agents Chemother 55:4933–4934. http://dx.doi.org/10.1128/AAC.00719-11.
146. Stoesser N, Sheppard AE, Peirano G, Sebra RP, Lynch T, Anson LW, Kasarskis A, Motyl MR, Crook DW, Pitout JD. 2016. First report of blaIMP-14 on a plasmid harboring multiple drug resistance genes in Escherichia coli sequence type 131. Antimicrob Agents Chemother 60:5068–5071. http://dx.doi.org/10.1128/AAC.00840-16.
147. Ortega A, Sáez D, Bautista V, Fernández-Romero S, Lara N, Aracil B, Pérez-Vázquez M, Campos J, Oteo J, Spanish Collaborating Group for the Antibiotic Resistance Surveillance Programme. 2016. Carbapenemase-producing Escherichia coli is becoming more prevalent in Spain mainly because of the polyclonal dissemination of OXA-48. J Antimicrob Chemother 71:2131–2138. http://dx.doi.org/10.1093/jac/dkw148.
148. O’Hara JA, Hu F, Ahn C, Nelson J, Rivera JI, Pasculle AW, Doi Y. 2014. Molecular epidemiology of KPC-producing Escherichia coli: occurrence of ST131-fimH30 subclone harboring pKpQIL-like IncFIIk plasmid. Antimicrob Agents Chemother 58:4234–4237. http://dx.doi.org/10.1128/AAC.02182-13.
149. Peirano G, Bradford PA, Kazmierczak KM, Badal RE, Hackel M, Hoban DJ, Pitout JD. 2014. Global incidence of carbapenemase-producing Escherichia coli ST131. Emerg Infect Dis 20:1928–1931. http://dx.doi.org/10.3201/eid2011.141388.
150. World Health Organization (WHO). 2014. Antimicrobial Resistance: Global Report on Surveillance 2014. WHO, Geneva, Switzerland.
151. Walther-Rasmussen J, Høiby N. 2007. Class A carbapenemases. J Antimicrob Chemother 60:470–482. http://dx.doi.org/10.1093/jac/dkm226. [PubMed]
152. Nordmann P, Cuzon G, Naas T. 2009. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 9:228–236. http://dx.doi.org/10.1016/S1473-3099(09)70054-4.
153. Chen L, Mathema B, Pitout JD, DeLeo FR, Kreiswirth BN. 2014. Epidemic Klebsiella pneumoniae ST258 is a hybrid strain. mBio 5:e01355-e14. http://dx.doi.org/10.1128/mBio.01355-14.
154. Chen L, Mathema B, Chavda KD, DeLeo FR, Bonomo RA, Kreiswirth BN. 2014. Carbapenemase-producing Klebsiella pneumoniae: molecular and genetic decoding. Trends Microbiol 22:686–696. http://dx.doi.org/10.1016/j.tim.2014.09.003.
155. Liu Y, Wan LG, Deng Q, Cao XW, Yu Y, Xu QF. 2015. First description of NDM-1-, KPC-2-, VIM-2- and IMP-4-producing Klebsiella pneumoniae strains in a single Chinese teaching hospital. Epidemiol Infect 143:376–384. http://dx.doi.org/10.1017/S0950268814000995.
156. Voulgari E, Gartzonika C, Vrioni G, Politi L, Priavali E, Levidiotou-Stefanou S, Tsakris A. 2014. The Balkan region: NDM-1-producing Klebsiella pneumoniae ST11 clonal strain causing outbreaks in Greece. J Antimicrob Chemother 69:2091–2097. http://dx.doi.org/10.1093/jac/dku105.
157. Stoesser N, Sheppard AE, Pankhurst L, De Maio N, Moore CE, Sebra R, Turner P, Anson LW, Kasarskis A, Batty EM, Kos V, Wilson DJ, Phetsouvanh R, Wyllie D, Sokurenko E, Manges AR, Johnson TJ, Price LB, Peto TE, Johnson JR, Didelot X, Walker AS, Crook DW, Modernizing Medical Microbiology Informatics Group (MMMIG). 2016. Evolutionary history of the global emergence of the Escherichia coli epidemic clone ST131. mBio 7:e02162. http://dx.doi.org/10.1128/mBio.02162-15.
158. Leekitcharoenphon P, Hendriksen RS, Le Hello S, Weill FX, Baggesen DL, Jun SR, Ussery DW, Lund O, Crook DW, Wilson DJ, Aarestrup FM. 2016. Global genomic epidemiology of Salmonella enterica serovar Typhimurium DT104. Appl Environ Microbiol 82:2516–2526. http://dx.doi.org/10.1128/AEM.03821-15.
159. Fothergill JL, Walshaw MJ, Winstanley C. 2012. Transmissible strains of Pseudomonas aeruginosa in cystic fibrosis lung infections. Eur Respir J 40:227–238. http://dx.doi.org/10.1183/09031936.00204411.
160. McCallum SJ, Gallagher MJ, Corkill JE, Hart CA, Ledson MJ, Walshaw MJ. 2002. Spread of an epidemic Pseudomonas aeruginosa strain from a patient with cystic fibrosis (CF) to non-CF relatives. Thorax 57:559–560. http://dx.doi.org/10.1136/thorax.57.6.559.
161. Brueggemann AB, Pai R, Crook DW, Beall B. 2007. Vaccine escape recombinants emerge after pneumococcal vaccination in the United States. PLoS Pathog 3:e168. http://dx.doi.org/10.1371/journal.ppat.0030168.
162. Henriques-Normark B, Blomberg C, Dagerhamn J, Bättig P, Normark S. 2008. The rise and fall of bacterial clones: Streptococcus pneumoniae. Nat Rev Microbiol 6:827–837. http://dx.doi.org/10.1038/nrmicro2011.
163. Nasser W, Beres SB, Olsen RJ, Dean MA, Rice KA, Long SW, Kristinsson KG, Gottfredsson M, Vuopio J, Raisanen K, Caugant DA, Steinbakk M, Low DE, McGeer A, Darenberg J, Henriques-Normark B, Van Beneden CA, Hoffmann S, Musser JM. 2014. Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences. Proc Natl Acad Sci U S A 111:E1768–E1776. http://dx.doi.org/10.1073/pnas.1403138111.
164. Ruer S, Pinotsis N, Steadman D, Waksman G, Remaut H. 2015. Virulence-targeted antibacterials: concept, promise, and susceptibility to resistance mechanisms. Chem Biol Drug Des 86:379–399. http://dx.doi.org/10.1111/cbdd.12517.
microbiolspec.MTBP-0013-2016.citations
cm/5/4
content/journal/microbiolspec/10.1128/microbiolspec.MTBP-0013-2016
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.MTBP-0013-2016
2017-07-27
2017-09-24

Abstract:

Ever since antibiotics were introduced into human and veterinary medicine to treat and prevent bacterial infections there has been a steady selection and increase in the frequency of antibiotic resistant bacteria. To be able to reduce the rate of resistance evolution, we need to understand how various biotic and abiotic factors interact to drive the complex processes of resistance emergence and transmission. We describe several of the fundamental factors that underlay resistance evolution, including rates and niches of emergence and persistence of resistant bacteria, time- and space-gradients of various selective agents, and rates and routes of transmission of resistant bacteria between humans, animals and other environments. Furthermore, we discuss the options available to reduce the rate of resistance evolution and/ or transmission and their advantages and disadvantages.

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

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Schematic view of the evolution of antibiotic resistance. Key questions in understanding the emergence and transmission include: (A) What are the origins of resistance genes? (B) Where do resistant pathogens emerge? (C) Which are the most significant selective pressures driving resistance evolution? (D) Which are the biological factors that influence rates of resistance development? (E) What are the routes, directions, and magnitudes of flow of pathogens between humans, animals, and the environment?

Source: microbiolspec July 2017 vol. 5 no. 4 doi:10.1128/microbiolspec.MTBP-0013-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Selection for antibiotic resistance occurs at several levels of complexity to generate a successful resistant clone.

Source: microbiolspec July 2017 vol. 5 no. 4 doi:10.1128/microbiolspec.MTBP-0013-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Effects of antibiotics on HGT and potential inhibition points.

Source: microbiolspec July 2017 vol. 5 no. 4 doi:10.1128/microbiolspec.MTBP-0013-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

Generic scheme for the creation and spread of globally successful antibiotic-resistant clones. In all environments (human, animal, and the wider environment), there are bacterial variants with resistance plasmids, resistance mutations, resistance genes, virulence genes, genes that increase transmission, etc. The mechanisms of HGT, coupled with selection by use of antibiotics, can select for combinations of these elements in one clone. When a clone arises that combines clinical resistance with high fitness and transmissibility, such a clone can spread through the global human population and become a dominant successful clone such as ST131 or ST258.

Source: microbiolspec July 2017 vol. 5 no. 4 doi:10.1128/microbiolspec.MTBP-0013-2016
Permissions and Reprints Request Permissions
Download as Powerpoint

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