Emergence and Spread of Antimicrobial Resistance: Recent Insights from Bacterial Population Genomics

  • Ulrich NübelEmail author
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 398)


Driven by progress of DNA sequencing technologies, recent population genomics studies have revealed that several bacterial pathogens constitute ‘measurably evolving populations’. As a consequence, it was possible to reconstruct the emergence and spatial spread of drug-resistant bacteria on the basis of temporally structured samples of bacterial genome sequences. Based on currently available data, some general inferences can be drawn across different bacterial species as follows:
  1. (1)

    Resistance to various antibiotics evolved years to decades earlier than had been anticipated on the basis of epidemiological surveillance data alone.

  2. (2)

    Resistance traits are more rapidly acquired than lost and commonly persist in bacterial populations for decades.

  3. (3)

    Global populations of drug-resistant pathogens are dominated by very few clones, yet the features enabling such spreading success have not been revealed, aside from antibiotic resistance.

  4. (4)

    Whole-genome sequencing proved very effective at identifying bacterial isolates as parts of the same transmission networks.



Fluoroquinolone Resistance Beijing Strain Bacterial Genome Sequence Colistin Resistance Spreading Success 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Aanensen DM, Feil EJ, Holden MT, Dordel J, Yeats CA, Fedosejev A, Goater R, Castillo-Ramirez S, Corander J, Colijn C, Chlebowicz MA, Schouls L, Heck M, Pluister G, Ruimy R, Kahlmeter G, Ahman J, Matuschek E, Friedrich AW, Parkhill J, Bentley SD, Spratt BG, Grundmann H, European SRLWG (2016) Whole-genome sequencing for routine pathogen surveillance in public health: a population snapshot of invasive Staphylococcus aureus in Europe. MBio 7(3):e00444-16CrossRefPubMedPubMedCentralGoogle Scholar
  2. Aarestrup FM, Koopmans MG (2016) Sharing data for global infectious disease surveillance and outbreak detection. Trends Microbiol 24(4):241–245CrossRefPubMedGoogle Scholar
  3. Accogli M, Giani T, Monaco M, Giufre M, Garcia-Fernandez 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(8):2293–2296CrossRefPubMedGoogle Scholar
  4. Adler A, Carmeli Y (2011) Dissemination of the Klebsiella pneumoniae carbapenemase in the health care settings: tracking the trails of an elusive offender. MBio 2(6):e00280-11Google Scholar
  5. Adler A, Khabra E, Paikin S, Carmeli Y (2016) Dissemination of the bla KPC gene by clonal spread and horizontal gene transfer: comparative study of incidence and molecular mechanisms. J Antimicrob ChemotherGoogle Scholar
  6. Alam MT, Read TD, Petit 3rd RA, Boyle-Vavra S, Miller LG, Eells SJ, Daum RS, David MZ (2015) Transmission and microevolution of USA300 MRSA in U.S. households: evidence from whole-genome sequencing. MBio 6(2):e00054Google Scholar
  7. Baines SL, Holt KE, Schultz MB, Seemann T, Howden BO, Jensen SO, van Hal SJ, Coombs GW, Firth N, Powell DR, Stinear TP, Howden BP (2015) Convergent adaptation in the dominant global hospital clone ST239 of methicillin-resistant Staphylococcus aureus. MBio 6(2):e00080CrossRefPubMedPubMedCentralGoogle Scholar
  8. Baldan R, Rancoita PM, Di Serio C, Mazzotti M, Cichero P, Ossi C, Biancardi A, Nizzero P, Saracco A, Scarpellini P, Cirillo DM (2015) Epidemic MRSA clone ST22-IV is more resistant to multiple host- and environment-related stresses compared with ST228-I. J Antimicrob Chemother 70(3):757–765CrossRefPubMedGoogle Scholar
  9. Bentley SD, Parkhill J (2015) Genomic perspectives on the evolution and spread of bacterial pathogens. Proc Biol Sci 282(1821):20150488CrossRefPubMedPubMedCentralGoogle Scholar
  10. Biek R, Pybus OG, Lloyd-Smith JO, Didelot X (2015) Measurably evolving pathogens in the genomic era. Trends Ecol Evol 30(6):306–313CrossRefPubMedPubMedCentralGoogle Scholar
  11. Black PA, de Vos M, Louw GE, van der Merwe RG, Dippenaar A, Streicher EM, Abdallah AM, Sampson SL, Victor TC, Dolby T, Simpson JA, van Helden PD, Warren RM, Pain A (2015) Whole genome sequencing reveals genomic heterogeneity and antibiotic purification in Mycobacterium tuberculosis isolates. BMC Genom 16(1):857CrossRefGoogle Scholar
  12. Bogdanovich T, Adams-Haduch JM, Tian GB, Nguyen MH, Kwak EJ, Muto CA, Doi Y (2011) Colistin-resistant, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae belonging to the international epidemic clone ST258. Clin Infect Dis 53(4):373–376CrossRefPubMedPubMedCentralGoogle Scholar
  13. Bradley P, Gordon NC, Walker TM, Dunn L, Heys S, Huang B, Earle S, Pankhurst LJ, Anson L, de Cesare M, Piazza P, Votintseva AA, Golubchik T, Wilson DJ, Wyllie DH, Diel R, Niemann S, Feuerriegel S, Kohl TA, Ismail N, Omar SV, Smith EG, Buck D, McVean G, Walker AS, Peto TE, Crook DW, Iqbal Z (2015) Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis. Nat Commun 6:10063CrossRefPubMedPubMedCentralGoogle Scholar
  14. Brites D, Gagneux S (2015) Co-evolution of Mycobacterium tuberculosis and Homo sapiens. Immunol Rev 264(1):6–24CrossRefPubMedPubMedCentralGoogle Scholar
  15. Carattoli A (2009) Resistance plasmid families in Enterobacteriaceae. Antimicrob Agents Chemother 53(6):2227–2238CrossRefPubMedPubMedCentralGoogle Scholar
  16. Casali N, Nikolayevskyy V, Balabanova Y, Ignatyeva O, Kontsevaya I, Harris SR, Bentley SD, Parkhill J, Nejentsev S, Hoffner SE, Horstmann RD, Brown T, Drobniewski F (2012) Microevolution of extensively drug-resistant tuberculosis in Russia. Genome Res 22(4):735–745CrossRefPubMedPubMedCentralGoogle Scholar
  17. Casali N, Nikolayevskyy V, Balabanova Y, Harris SR, Ignatyeva O, Kontsevaya I, Corander J, Bryant J, Parkhill J, Nejentsev S, Horstmann RD, Brown T, Drobniewski F (2014) Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat Genet 46(3):279–286CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cegielski JP (2010) Extensively drug-resistant tuberculosis: “there must be some kind of way out of here”. Clin Infect Dis 50(Suppl 3):S195–S200CrossRefPubMedGoogle Scholar
  19. Chambers HF, Deleo FR (2009) Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol 7(9):629–641CrossRefPubMedPubMedCentralGoogle Scholar
  20. Chen L, Mathema B, Pitout JD, DeLeo FR, Kreiswirth BN (2014) Epidemic Klebsiella pneumoniae ST258 is a hybrid strain. MBio 5(3):e01355-01314CrossRefGoogle Scholar
  21. Comas I, Borrell S, Roetzer A, Rose G, Malla B, Kato-Maeda M, Galagan J, Niemann S, Gagneux S (2012) Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet 44(1):106–110CrossRefGoogle Scholar
  22. Falgenhauer L, Waezsada SE, Yao Y, Imirzalioglu C, Kasbohrer A, Rösler U, Michael GB, Schwarz S, Werner G, Kreienbrock L, Chakraborty T, Consortium, R (2016) Colistin resistance gene mcr-1 in extended-spectrum beta-lactamase-producing and carbapenemase-producing Gram-negative bacteria in Germany. Lancet Infect Dis S1473-3099(16): 00009-00008Google Scholar
  23. Cooper BS, Kypraios T, Batra R, Wyncoll D, Tosas O, Edgeworth JD (2012) Quantifying type-specific reproduction numbers for nosocomial pathogens: evidence for heightened transmission of an Asian sequence type 239 MRSA clone. PLoS Comput Biol 8(4):e1002454CrossRefPubMedPubMedCentralGoogle Scholar
  24. Crisóstomo MI, Westh H, Tomasz A, Chung M, Oliveira DC, de Lencastre H (2001) The evolution of methicillin resistance in Staphylococcus aureus: similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones. Proc Natl Acad Sci USA 98(17):9865–9870CrossRefPubMedPubMedCentralGoogle Scholar
  25. Croucher NJ, Didelot X (2015) The application of genomics to tracing bacterial pathogen transmission. Curr Opin Microbiol 23:62–67CrossRefPubMedGoogle Scholar
  26. Croucher NJ, Klugman KP (2014) The emergence of bacterial “hopeful monsters”. MBio 5(4):e01550-01514CrossRefGoogle Scholar
  27. Cui Y, Yang X, Didelot X, Guo C, Li D, Yan Y, Zhang Y, Yuan Y, Yang H, Wang J, Wang J, Song Y, Zhou D, Falush D, Yang R (2015) Epidemic clones, oceanic gene pools, and eco-LD in the free living marine pathogen Vibrio parahaemolyticus. Mol Biol Evol 32(6):1396–1410CrossRefPubMedGoogle Scholar
  28. Cuny C, Köck R, Witte W (2013) Livestock associated MRSA (LA-MRSA) and its relevance for humans in Germany. Int J Med Microbiol 303(6–7):331–337CrossRefPubMedGoogle Scholar
  29. David MZ, Daum RS (2010) Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev 23(3):616–687CrossRefPubMedPubMedCentralGoogle Scholar
  30. DeLeo FR, Chambers HF (2009) Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. J Clin Invest 119(9):2464–2474CrossRefPubMedPubMedCentralGoogle Scholar
  31. DeLeo FR, Otto M, Kreiswirth BN, Chambers HF (2010) Community-associated meticillin-resistant Staphylococcus aureus. Lancet 375(9725):1557–1568CrossRefPubMedPubMedCentralGoogle Scholar
  32. DeLeo FR, Chen L, Porcella SF, Martens CA, Kobayashi SD, Porter AR, Chavda KD, Jacobs MR, Mathema B, Olsen RJ, Bonomo RA, Musser JM, Kreiswirth BN (2014) Molecular dissection of the evolution of carbapenem-resistant multilocus sequence type 258 Klebsiella pneumoniae. Proc Natl Acad Sci USA 111(13):4988–4993CrossRefPubMedPubMedCentralGoogle Scholar
  33. Didelot X, Bowden R, Wilson DJ, Peto TE, Crook DW (2012) Transforming clinical microbiology with bacterial genome sequencing. Nat Rev Genet 13(9):601–612CrossRefPubMedPubMedCentralGoogle Scholar
  34. Didelot X, Gardy J, Colijn C (2014) Bayesian inference of infectious disease transmission from whole-genome sequence data. Mol Biol Evol 31(7):1869–1879CrossRefPubMedPubMedCentralGoogle Scholar
  35. Dippenaar A, Warren RM (2015) Fighting an old disease with next-generation sequencing. Elife 4:e06782Google Scholar
  36. Drummond AJ, Pybus OG, Rambaut A, Forsberg R, Rodrigo AG (2003) Measurably evolving populations. Trends Ecol Evol 18:481CrossRefGoogle Scholar
  37. Earle SG, Wu C-H, Charlesworth J, Stoesser N, Gordon NC, Walker AS, Spencer CCA, Iqbal Z, Clifton DA, Hopkins KL, Woodford N, Smith EG, Imail N, Llewelyn MJ, Peto TE, Crook DW, McVean G, Walker AS, Wilson D (2016) Identifying lineage effects when controlling for population structure improves power in bacterial association studies. Nature Microbiology 1:e16041CrossRefGoogle Scholar
  38. Eldholm V, Monteserin J, Rieux A, Lopez B, Sobkowiak B, Ritacco V, Balloux F (2015) Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain. Nat Commun 6:7119CrossRefPubMedPubMedCentralGoogle Scholar
  39. Eyre DW, Golubchik T, Gordon NC, Bowden R, Piazza P, Batty EM, Ip CL, Wilson DJ, Didelot X, O’Connor L, Lay R, Buck D, Kearns AM, Shaw A, Paul J, Wilcox MH, Donnelly PJ, Peto TE, Walker AS, Crook DW (2012) A pilot study of rapid benchtop sequencing of Staphylococcus aureus and Clostridium difficile for outbreak detection and surveillance. BMJ Open 2(3):e001124CrossRefPubMedPubMedCentralGoogle Scholar
  40. Farhat MR, Shapiro BJ, Kieser KJ, Sultana R, Jacobson KR, Victor TC, Warren RM, Streicher EM, Calver A, Sloutsky A, Kaur D, Posey JE, Plikaytis B, Oggioni MR, Gardy JL, Johnston JC, Rodrigues M, Tang PK, Kato-Maeda M, Borowsky ML, Muddukrishna B, Kreiswirth BN, Kurepina N, Galagan J, Gagneux S, Birren B, Rubin EJ, Lander ES, Sabeti PC, Murray M (2013) Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. Nat Genet 45(10):1183–1189CrossRefPubMedPubMedCentralGoogle Scholar
  41. Feil EJ (2015) Toward a synthesis of genotypic typing and phenotypic inference in the genomics era. Future Microbiol 10(12):1897–1899CrossRefPubMedGoogle Scholar
  42. Ford CB, Lin PL, Chase MR, Shah RR, Iartchouk O, Galagan J, Mohaideen N, Ioerger TR, Sacchettini JC, Lipsitch M, Flynn JL, Fortune SM (2011) Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet 43(5):482–486CrossRefPubMedPubMedCentralGoogle Scholar
  43. Fraser C, Hanage WP, Spratt BG (2005) Neutral microepidemic evolution of bacterial pathogens. Proc Natl Acad Sci USA 102(6):1968–1973CrossRefPubMedPubMedCentralGoogle Scholar
  44. Golubchik T, Batty EM, Miller RR, Farr H, Young BC, Larner-Svensson H, Fung R, Godwin H, Knox K, Votintseva A, Everitt RG, Street T, Cule M, Ip CL, Didelot X, Peto TE, Harding RM, Wilson DJ, Crook DW, Bowden R (2013) Within-host evolution of Staphylococcus aureus during asymptomatic carriage. PLoS ONE 8(5):e61319CrossRefPubMedPubMedCentralGoogle Scholar
  45. Gordon NC, Price JR, Cole K, Everitt R, Morgan M, Finney J, Kearns AM, Pichon B, Young B, Wilson DJ, Llewelyn MJ, Paul J, Peto TE, Crook DW, Walker AS, Golubchik T (2014) Prediction of Staphylococcus aureus antimicrobial resistance by whole-genome sequencing. J Clin Microbiol 52(4):1182–1191CrossRefPubMedPubMedCentralGoogle Scholar
  46. Guerra-Assunção JA, Crampin AC, Houben RM, Mzembe T, Mallard K, Coll F, Khan P, Banda L, Chiwaya A, Pereira RP, McNerney R, Fine PE, Parkhill J, Clark TG, Glynn JR (2015a) Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area. Elife 4:e05166Google Scholar
  47. Guerra-Assunção JA, Houben RM, Crampin AC, Mzembe T, Mallard K, Coll F, Khan P, Banda L, Chiwaya A, Pereira RP, McNerney R, Harris D, Parkhill J, Clark TG, Glynn JR (2015b) Recurrence due to relapse or reinfection with Mycobacterium tuberculosis: a whole-genome sequencing approach in a large, population-based cohort with a high HIV infection prevalence and active follow-up. J Infect Dis 211(7):1154–1163CrossRefPubMedGoogle Scholar
  48. Gutierrez-Vazquez JM (1956) Studies on the rate of growth of mycobacteria. I. Generation time of Mycobacterium tuberculosis on several solid and liquid media and effects exerted by glycerol and malachite green. Am Rev Tuberc 74(1):50–58PubMedGoogle Scholar
  49. Haller S, Eller C, Hermes J, Kaase M, Steglich M, Radonic A, Dabrowski PW, Nitsche A, Pfeifer Y, Werner G, Wunderle W, Velasco E, Abu-Sin M, Eckmanns T, Nübel U (2015) What caused the outbreak of ESBL producing Klebsiella pneumoniae in a neonatal intensive care unit, Germany 2009 to 2012? Reconstructing transmission with epidemiological analysis and whole-genome sequencing. BMJ Open 5:e007397CrossRefPubMedPubMedCentralGoogle Scholar
  50. Harris SR, Feil EJ, Holden MT, Quail MA, Nickerson EK, Chantratita N, Gardete S, Tavares A, Day N, Lindsay JA, Edgeworth JD, de Lencastre H, Parkhill J, Peacock SJ, Bentley SD (2010) Evolution of MRSA during hospital transmission and intercontinental spread. Science 327(5964):469–474CrossRefPubMedPubMedCentralGoogle Scholar
  51. Hasman H, Hammerum AM, Hansen F, Hendriksen RS, Olesen B, Agerso Y, Zankari E, Leekitcharoenphon P, Stegger M, Kaas RS, Cavaco LM, Hansen DS, Aarestrup FM, Skov RL (2015) Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015. Euro Surveill 20(49):1–5Google Scholar
  52. Hawkey PM (1997) Quinolones in sweat and quinolone resistance. Lancet 349(9046):148–149CrossRefPubMedGoogle Scholar
  53. Holden MT, Hsu LY, Kurt K, Weinert LA, Mather AE, Harris SR, Strommenger B, Layer F, Witte W, de Lencastre H, Skov R, Westh H, Zemlickova H, Coombs G, Kearns AM, Hill RL, Edgeworth J, Gould I, Gant V, Cooke J, Edwards GF, McAdam PR, Templeton KE, McCann A, Zhou Z, Castillo-Ramirez S, Feil EJ, Hudson LO, Enright MC, Balloux F, Aanensen DM, Spratt BG, Fitzgerald JR, Parkhill J, Achtman M, Bentley SD, Nübel U (2013) A genomic portrait of the emergence, evolution and global spread of a methicillin resistant Staphylococcus aureus pandemic. Genome Res 23:653–664CrossRefPubMedPubMedCentralGoogle Scholar
  54. Holt KE, Wertheim H, Zadoks RN, Baker S, Whitehouse CA, Dance D, Jenney A, Connor TR, Hsu LY, Severin J, Brisse S, Cao H, Wilksch J, Gorrie C, Schultz MB, Edwards DJ, Nguyen KV, Nguyen TV, Dao TT, Mensink M, Minh VL, Nhu NT, Schultsz C, Kuntaman K, Newton PN, Moore CE, Strugnell RA, Thomson NR (2015) Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health. Proc Natl Acad Sci USA 112(27):E3574-3581CrossRefGoogle Scholar
  55. Jevons MP (1961) Celbenin-resistant staphylococci. Brit Med J 1:124–125CrossRefPubMedCentralGoogle Scholar
  56. Johnson, AP (2011) Methicillin-resistant Staphylococcus aureus: the European landscape. J Antimicrob Chemother 66(Suppl 4):iv43-iv48Google Scholar
  57. 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(2):e00272-15Google Scholar
  58. Jombart T, Cori A, Didelot X, Cauchemez S, Fraser C, Ferguson N (2014) Bayesian reconstruction of disease outbreaks by combining epidemiologic and genomic data. PLoS Comput Biol 10(1):e1003457CrossRefPubMedPubMedCentralGoogle Scholar
  59. Baym M, Stone LK, Kishony, R (2016) Multidrug evolutionary strategies to reverse antibiotic resistance. Science 351(6268):aad3292Google Scholar
  60. Knight GM, Budd EL, Whitney L, Thornley A, Al-Ghusein H, Planche T, Lindsay JA (2012) Shift in dominant hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) clones over time. J Antimicrob Chemother 67(10):2514–2522CrossRefPubMedGoogle Scholar
  61. Köser CU, Holden MTG, Ellington MJ, Cartwright EJP, Brown NM, Ogilvy-Stuart AL, Hsu LY, Chewapreecha C, Croucher NJ, Harris SR, Sanders M, Enright MC, Dougan G, Bentley SD, Schulz-Trieglaff OB, Smith GP, Peacock SJ (2012) Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N Engl J Med 366:2267–2275CrossRefPubMedPubMedCentralGoogle Scholar
  62. Kutumbaka KK, Han S, Mategko J, Nadala C, Buser GL, Cassidy MP, Beldavs ZG, Weissman SJ, Morey KE, Vega R, Samadpour M (2014) Draft genome sequence of blaNDM-1-positive Escherichia coli O25b-ST131 clone isolated from an environmental sample. Genome Announc 2(3):e00462-14Google Scholar
  63. Laabei M, Recker M, Rudkin JK, Aldeljawi M, Gulay Z, Sloan TJ, Williams P, Endres JL, Bayles KW, Fey PD, Yajjala VK, Widhelm T, Hawkins E, Lewis K, Parfett S, Scowen L, Peacock SJ, Holden M, Wilson D, Read TD, van den Elsen J, Priest NK, Feil EJ, Hurst LD, Josefsson E, Massey RC (2014) Predicting the virulence of MRSA from its genome sequence. Genome Res 24(5):839–849CrossRefPubMedPubMedCentralGoogle Scholar
  64. Laabei M, Uhlemann AC, Lowy FD, Austin ED, Yokoyama M, Ouadi K, Feil E, Thorpe HA, Williams B, Perkins M, Peacock SJ, Clarke SR, Dordel J, Holden M, Votintseva AA, Bowden R, Crook DW, Young BC, Wilson DJ, Recker M, Massey RC (2015) Evolutionary trade-offs underlie the multi-faceted virulence of Staphylococcus aureus. PLoS Biol 13(9):e1002229CrossRefPubMedPubMedCentralGoogle Scholar
  65. Luo T, Comas I, Luo D, Lu B, Wu J, Wei L, Yang C, Liu Q, Gan M, Sun G, Shen X, Liu F, Gagneux S, Mei J, Lan R, Wan K, Gao Q (2015) Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese. Proc Natl Acad Sci USA 112(26):8136–8141CrossRefPubMedPubMedCentralGoogle Scholar
  66. 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(3):565–591CrossRefPubMedPubMedCentralGoogle Scholar
  67. McAdam PR, Templeton KE, Edwards GF, Holden MT, Feil EJ, Aanensen DM, Bargawi HJ, Spratt BG, Bentley SD, Parkhill J, Enright MC, Holmes A, Girvan EK, Godfrey PA, Feldgarden M, Kearns AM, Rambaut A, Robinson DA, Fitzgerald JR (2012) Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus. Proc Natl Acad Sci USA 109(23):9107–9112CrossRefPubMedPubMedCentralGoogle Scholar
  68. Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, Willery E, Blum MG, Rusch-Gerdes S, Mokrousov I, Aleksic E, Allix-Beguec C, Antierens A, Augustynowicz-Kopec E, Ballif M, Barletta F, Beck HP, Barry CE 3rd, Bonnet M, Borroni E, Campos-Herrero I, Cirillo D, Cox H, Crowe S, Crudu V, Diel R, Drobniewski F, Fauville-Dufaux M, Gagneux S, Ghebremichael S, Hanekom M, Hoffner S, Jiao WW, Kalon S, Kohl TA, Kontsevaya I, Lillebaek T, Maeda S, Nikolayevskyy V, Rasmussen M, Rastogi N, Samper S, Sanchez-Padilla E, Savic B, Shamputa IC, Shen A, Sng LH, Stakenas P, Toit K, Varaine F, Vukovic D, Wahl C, Warren R, Supply P, Niemann S, Wirth T (2015) Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet 47(3):242–249CrossRefPubMedGoogle Scholar
  69. Morelli MJ, Thebaud G, Chadoeuf J, King DP, Haydon DT, Soubeyrand S (2012) A Bayesian inference framework to reconstruct transmission trees using epidemiological and genetic data. PLoS Comput Biol 8(11):e1002768CrossRefPubMedPubMedCentralGoogle Scholar
  70. Morris D, McGarry E, Cotter M, Passet V, Lynch M, Ludden C, Hannan MM, Brisse S, Cormican M (2012) Detection of OXA-48 carbapenemase in the pandemic clone Escherichia coli O25b:H4-ST131 in the course of investigation of an outbreak of OXA-48-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 56(7):4030–4031CrossRefPubMedPubMedCentralGoogle Scholar
  71. Munoz-Price LS, Poirel L, Bonomo RA, Schwaber MJ, Daikos GL, Cormican M, Cornaglia G, Garau J, Gniadkowski M, Hayden MK, Kumarasamy K, Livermore DM, Maya JJ, Nordmann P, Patel JB, Paterson DL, Pitout J, Villegas MV, Wang H, Woodford N, Quinn JP (2013) Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 13(9):785–796CrossRefPubMedPubMedCentralGoogle Scholar
  72. Nübel U, Roumagnac P, Feldkamp M, Song JH, Ko KS, Huang YC, Coombs G, Ip M, Westh H, Skov R, Struelens MJ, Goering RV, Strommenger B, Weller A, Witte W, Achtman M (2008) Frequent emergence and limited geographic dispersal of methicillin-resistant Staphylococcus aureus. Proc Natl Acad Sci USA 105:14130–14135CrossRefPubMedPubMedCentralGoogle Scholar
  73. Nübel U, Dordel J, Kurt K, Strommenger B, Westh H, Shukla SK, Zemlickova H, Leblois R, Wirth T, Jombart T, Balloux F, Witte W (2010) A timescale for evolution, population expansion, and spatial spread of an emerging clone of methicillin-resistant Staphylococcus aureus. PLoS Pathog 6(4):e1000855CrossRefPubMedPubMedCentralGoogle Scholar
  74. Nübel U, Strommenger B, Layer F, Witte W (2011) From types to trees: reconstructing the spatial spread of Staphylococcus aureus based on DNA variation. Int J Med Microbiol 301:614–618CrossRefPubMedGoogle Scholar
  75. Nübel U, Nachtnebel M, Falkenhorst G, Benzler J, Hecht J, Kube M, Brocker F, Moelling K, Buhrer C, Gastmeier P, Piening B, Behnke M, Dehnert M, Layer F, Witte W, Eckmanns T (2013) MRSA transmission on a neonatal intensive care unit: epidemiological and genome-based phylogenetic analyses. PLoS ONE 8(1):e54898CrossRefPubMedPubMedCentralGoogle Scholar
  76. Paterson GK, Harrison EM, Murray GG, Welch JJ, Warland JH, Holden MT, Morgan FJ, Ba X, Koop G, Harris SR, Maskell DJ, Peacock SJ, Herrtage ME, Parkhill J, Holmes MA (2015) Capturing the cloud of diversity reveals complexity and heterogeneity of MRSA carriage, infection and transmission. Nat Commun 6:6560CrossRefPubMedPubMedCentralGoogle Scholar
  77. Peirano G, Schreckenberger PC, Pitout JD (2011) Characteristics of NDM-1-producing Escherichia coli isolates that belong to the successful and virulent clone ST131. Antimicrob Agents Chemother 55(6):2986–2988CrossRefPubMedPubMedCentralGoogle Scholar
  78. Petty NK, Ben Zakour NL, Stanton-Cook M, Skippington E, Totsika M, Forde BM, Phan MD, Gomes Moriel D, Peters KM, Davies M, Rogers BA, Dougan G, Rodriguez-Bano J, Pascual A, Pitout JD, Upton M, Paterson DL, Walsh TR, Schembri MA, Beatson SA (2014) Global dissemination of a multidrug resistant Escherichia coli clone. Proc Natl Acad Sci USA 111(15):5694–5699CrossRefPubMedPubMedCentralGoogle Scholar
  79. 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-beta-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. MBio 4(6):e00377-00313CrossRefGoogle Scholar
  80. Reuter S, Ellington MJ, Cartwright EJ, Koser CU, Torok ME, Gouliouris T, Harris SR, Brown NM, Holden MT, Quail M, Parkhill J, Smith GP, Bentley SD, Peacock SJ (2013) Rapid bacterial whole-genome sequencing to enhance diagnostic and public health microbiology. JAMA Intern Med 173(15):1397–1404CrossRefPubMedPubMedCentralGoogle Scholar
  81. Reuter S, Torok ME, Holden MT, Reynolds R, Raven KE, Blane B, Donker T, Bentley SD, Aanensen DM, Grundmann H, Feil EJ, Spratt BG, Parkhill J, Peacock SJ (2016) Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland. Genome Res 26(2):263–270CrossRefPubMedPubMedCentralGoogle Scholar
  82. Richardson JF, Reith S (1993) Characterization of a strain of methicillin-resistant Staphylococcus aureus (EMRSA-15) by conventional and molecular methods. J Hosp Infect 25(1):45–52CrossRefPubMedGoogle Scholar
  83. Robinson DA, Enright MC (2004) Multilocus sequence typing and the evolution of methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect 10(2):92–97CrossRefPubMedGoogle Scholar
  84. Roetzer A, Diel R, Kohl TA, Ruckert C, Nübel U, Blom J, Wirth T, Jaenicke S, Schuback S, Rusch-Gerdes S, Supply P, Kalinowski J, Niemann S (2013) Whole genome sequencing versus traditional genotyping for investigation of a Mycobacterium tuberculosis outbreak: a longitudinal molecular epidemiological study. PLoS Med 10(2):e1001387CrossRefPubMedPubMedCentralGoogle Scholar
  85. Sheppard SK, Didelot X, Meric G, Torralbo A, Jolley KA, Kelly DJ, Bentley SD, Maiden MC, Parkhill J, Falush D (2013) Genome-wide association study identifies vitamin B5 biosynthesis as a host specificity factor in Campylobacter. Proc Natl Acad Sci USA 110(29):11923–11927CrossRefPubMedPubMedCentralGoogle Scholar
  86. Sintchenko V, Holmes EC (2015) The role of pathogen genomics in assessing disease transmission. BMJ 350:h1314CrossRefPubMedGoogle Scholar
  87. Snitkin ES, Zelazny AM, Thomas PJ, Stock F, Group NCSP, Henderson DK, Palmore TN, Segre JA (2012) Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med 4(148):148ra116Google Scholar
  88. Srivastava S, Pasipanodya JG, Meek C, Leff R, Gumbo T (2011) Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability. J Infect Dis 204(12):1951–1959CrossRefPubMedPubMedCentralGoogle Scholar
  89. Stoesser N, Giess A, Batty EM, Sheppard AE, Walker AS, Wilson DJ, Didelot X, Bashir A, Sebra R, Kasarskis A, Sthapit B, Shakya M, Kelly D, Pollard AJ, Peto TE, Crook DW, Donnelly P, Thorson S, Amatya P, Joshi S (2014) Genome sequencing of an extended series of NDM-producing Klebsiella pneumoniae isolates from neonatal infections in a Nepali hospital characterizes the extent of community- versus hospital-associated transmission in an endemic setting. Antimicrob Agents Chemother 58(12):7347–7357CrossRefPubMedPubMedCentralGoogle Scholar
  90. Stoesser N, Sheppard AE, Moore CE, Golubchik T, Parry CM, Nget P, Saroeun M, Day NP, Giess A, Johnson JR, Peto TE, Crook DW, Walker AS, Modernizing Medical Microbiology Informatics G (2015) Extensive within-host diversity in fecally carried extended-spectrum-beta-lactamase-producing Escherichia coli isolates: implications for transmission analyses. J Clin Microbiol 53(7):2122–2131Google Scholar
  91. 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 G (2016) Evolutionary history of the global emergence of the Escherichia coli epidemic clone ST131. MBio 7(2):e02162Google Scholar
  92. Strommenger B, Bartels MD, Kurt K, Layer F, Rohde SM, Boye K, Westh H, Witte W, De Lencastre H, Nübel U (2014) Evolution of methicillin-resistant Staphylococcus aureus towards increasing resistance. J Antimicrob Chemother 69(3):616–622CrossRefPubMedGoogle Scholar
  93. Temkin E, Adler A, Lerner A, Carmeli Y (2014) Carbapenem-resistant enterobacteriaceae: biology, epidemiology, and management. Ann NY Acad Sci 1323:22–42CrossRefPubMedGoogle Scholar
  94. Tong SY, Holden MT, Nickerson EK, Cooper BS, Koser CU, Cori A, Jombart T, Cauchemez S, Fraser C, Wuthiekanun V, Thaipadungpanit J, Hongsuwan M, Day NP, Limmathurotsakul D, Parkhill J, Peacock SJ (2015) Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting. Genome Res 25(1):111–118CrossRefPubMedPubMedCentralGoogle Scholar
  95. Uhlemann AC, Dordel J, Knox JR, Raven KE, Parkhill J, Holden MT, Peacock SJ, Lowy FD (2014) Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community. Proc Natl Acad Sci USA 111(18):6738–6743CrossRefPubMedPubMedCentralGoogle Scholar
  96. van Dijk EL, Auger H, Jaszczyszyn Y, Thermes C (2014) Ten years of next-generation sequencing technology. Trends Genet 30(9):418–426CrossRefPubMedGoogle Scholar
  97. Walker TM, Ip CL, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, Eyre DW, Wilson DJ, Hawkey PM, Crook DW, Parkhill J, Harris D, Walker AS, Bowden R, Monk P, Smith EG, Peto TE (2013) Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis 13(2):137–146CrossRefPubMedPubMedCentralGoogle Scholar
  98. Weber SG, Gold HS, Hooper DC, Karchmer AW, Carmeli Y (2003) Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients. Emerg Infect Dis 9(11):1415–1422CrossRefPubMedPubMedCentralGoogle Scholar
  99. WHO (2015) Global tuberculosis report. World Health Organization, GenevaGoogle Scholar
  100. Woerther PL, Burdet C, Chachaty E, Andremont A (2013) Trends in human fecal carriage of extended-spectrum beta-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev 26(4):744–758CrossRefPubMedPubMedCentralGoogle Scholar
  101. Woodford N, Turton JF, Livermore DM (2011) Multiresistant Gram-negative bacteria: the role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol Rev 35(5):736–755CrossRefPubMedGoogle Scholar
  102. Worby CJ, Lipsitch M, Hanage WP (2014) Within-host bacterial diversity hinders accurate reconstruction of transmission networks from genomic distance data. PLoS Comput Biol 10(3):e1003549CrossRefPubMedPubMedCentralGoogle Scholar
  103. Wyres KL, Gorrie C, Edwards DJ, Wertheim HF, Hsu LY, Van Kinh N, Zadoks R, Baker S, Holt KE (2015) Extensive capsule locus variation and large-scale genomic recombination within the Klebsiella pneumoniae clonal group 258. Genome Biol Evol 7(5):1267–1279CrossRefPubMedPubMedCentralGoogle Scholar
  104. Young BC, Golubchik T, Batty EM, Fung R, Larner-Svensson H, Votintseva AA, Miller RR, Godwin H, Knox K, Everitt RG, Iqbal Z, Rimmer AJ, Cule M, Ip CL, Didelot X, Harding RM, Donnelly P, Peto TE, Crook DW, Bowden R, Wilson DJ (2012) Evolutionary dynamics of Staphylococcus aureus during progression from carriage to disease. Proc Natl Acad Sci USA 109(12):4550–4555CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.DZIF Group on Microbial Genome ResearchLeibniz Institute DSMZBraunschweigGermany
  2. 2.Technical University BraunschweigBraunschweigGermany
  3. 3.German Center for Infection Research (DZIF), Partner Site Hannover-BraunschweigBraunschweigGermany

Personalised recommendations