1887

Abstract

Bacteraemia caused by Escherichia coli is a growing problem with a significant mortality. The factors that influence the acquisition and outcome of these infections are not clear. Here, we have linked detailed genetic data from the whole-genome sequencing of 162 bacteraemic isolates collected in Scotland, UK, in 2013–2015, with clinical data in order to delineate bacterial and host factors that influence the acquisition in hospital or the community, outcome and antibiotic resistance. We identified four major sequence types (STs) in these isolates: ST131, ST69, ST73 and ST95. Nearly 50 % of the bacteraemic isolates had a urinary origin. ST69 was genetically distinct from the other STs, with significantly less sharing of accessory genes and with a distinct plasmid population. Virulence genes were widespread and diversely distributed between the dominant STs. ST131 was significantly associated with hospital-associated infections (HAIs), and ST69 with those from the community. However, there was no association of ST with outcome, although patients with HAI had a higher immediate mortality compared to those with community-associated infections (CAIs). Genome-wide association studies revealed genes involved in antibiotic persistence as significantly associated with HAIs and those encoding elements of a type VI secretion system with CAIs. Antibiotic resistance was common, and there were networks of correlated resistance genes and phenotypic antibiotic resistance. This study has revealed the complex interactions between the genotype of E. coli and its ability to cause bacteraemia, and some of the determinants influencing hospital or community acquisition. In part, these are shaped by antibiotic usage, but strain-specific factors are also important.

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2018-06-22
2024-04-19
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References

  1. Poolman JT, Wacker M. Extraintestinal pathogenic Escherichia coli, a common human pathogen: challenges for vaccine development and progress in the field. J Infect Dis 2016; 213:6–13 [View Article][PubMed]
    [Google Scholar]
  2. Dale AP, Woodford N. Extra-intestinal pathogenic Escherichia coli (ExPEC): disease, carriage and clones. J Infect 2015; 71:615–626 [View Article][PubMed]
    [Google Scholar]
  3. Laupland KB. Incidence of bloodstream infection: a review of population-based studies. Clin Microbiol Infect 2013; 19:492–500 [View Article][PubMed]
    [Google Scholar]
  4. de Kraker ME, Jarlier V, Monen JC, Heuer OE, van de Sande N et al. The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. Clin Microbiol Infect 2013; 19:860–868 [View Article][PubMed]
    [Google Scholar]
  5. Søgaard M, Nørgaard M, Dethlefsen C, Schønheyder HC. Temporal changes in the incidence and 30-day mortality associated with bacteremia in hospitalized patients from 1992 through 2006: a population-based cohort study. Clin Infect Dis 2011; 52:61–69 [View Article][PubMed]
    [Google Scholar]
  6. Abernethy JK, Johnson AP, Guy R, Hinton N, Sheridan EA et al. Thirty day all-cause mortality in patients with Escherichia coli bacteraemia in England. Clin Microbiol Infect 2015; 21:251.e1–25251 [View Article][PubMed]
    [Google Scholar]
  7. Roubaud Baudron C, Panhard X, Clermont O, Mentré F, Fantin B et al. Escherichia coli bacteraemia in adults: age-related differences in clinical and bacteriological characteristics, and outcome. Epidemiol Infect 2014; 142:2672–2683 [View Article][PubMed]
    [Google Scholar]
  8. Thelwall S, Nsonwu N, Bhattacharya A, Wasti S, Gerver S et al. Annual Epidemiological Commentary: Mandatory MRSA, MSSA and E. coli Bacteraemia and C. difficile Infection Data 2016/17 document no. 2017158. London:: Public Health England; 2017
    [Google Scholar]
  9. Health Protection Scotland Scottish National Point Prevalence Survey of Healthcare Associated Infection and Antimicrobial Prescribing 2016. Glasgow:: Health Protection Scotland; 2017
    [Google Scholar]
  10. Health Protection Scotland Healthcare Associated Infections 2016. Glasgow:: Health Protection Scotland; 2017
    [Google Scholar]
  11. Abernethy J, Guy R, Sheridan EA, Hopkins S, Kiernan M et al. Epidemiology of Escherichia coli bacteraemia in England: results of an enhanced sentinel surveillance programme. J Hosp Infect 2017; 95:365–375 [View Article][PubMed]
    [Google Scholar]
  12. Schlackow I, Stoesser N, Walker AS, Crook DW, Peto TE et al. Increasing incidence of Escherichia coli bacteraemia is driven by an increase in antibiotic-resistant isolates: electronic database study in Oxfordshire 1999– 2011. J Antimicrob Chemother 2012; 67:1514–1524 [View Article][PubMed]
    [Google Scholar]
  13. Day MJ, Doumith M, Abernethy J, Hope R, Reynolds R et al. Population structure of Escherichia coli causing bacteraemia in the UK and Ireland between 2001 and 2010. J Antimicrob Chemother 2016; 71:2139–2142 [View Article][PubMed]
    [Google Scholar]
  14. Horner C, Fawley W, Morris K, Parnell P, Denton M et al. Escherichia coli bacteraemia: 2 years of prospective regional surveillance (2010–12). J Antimicrob Chemother 2014; 69:91–100 [View Article][PubMed]
    [Google Scholar]
  15. Banerjee R, Johnston B, Lohse C, Chattopadhyay S, Tchesnokova V et al. The clonal distribution and diversity of extraintestinal Escherichia coli isolates vary according to patient characteristics. Antimicrob Agents Chemother 2013; 57:5912–5917 [View Article][PubMed]
    [Google Scholar]
  16. Adams-Sapper S, Diep BA, Perdreau-Remington F, Riley LW. Clonal composition and community clustering of drug-susceptible and -resistant Escherichia coli isolates from bloodstream infections. Antimicrob Agents Chemother 2013; 57:490–497 [View Article][PubMed]
    [Google Scholar]
  17. Gibreel TM, Dodgson AR, Cheesbrough J, Fox AJ, Bolton FJ et al. Population structure, virulence potential and antibiotic susceptibility of uropathogenic Escherichia coli from Northwest England. J Antimicrob Chemother 2012; 67:346–356 [View Article][PubMed]
    [Google Scholar]
  18. Riley LW. Pandemic lineages of extraintestinal pathogenic Escherichia coli . Clin Microbiol Infect 2014; 20:380–390 [View Article][PubMed]
    [Google Scholar]
  19. Nicolas-Chanoine MH, Bertrand X, Madec JY. Escherichia coli ST131, an intriguing clonal group. Clin Microbiol Rev 2014; 27:543–574 [View Article][PubMed]
    [Google Scholar]
  20. Kallonen T, Brodrick HJ, Harris SR, Corander J, Brown NM et al. Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131. Genome Res 2017;; 27:1437–1449 [View Article][PubMed]
    [Google Scholar]
  21. Inouye M, Dashnow H, Raven LA, Schultz MB, Pope BJ et al. SRST2: rapid genomic surveillance for public health and hospital microbiology labs. Genome Med 2014; 6:90 [View Article][PubMed]
    [Google Scholar]
  22. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009; 25:2078–2079 [View Article][PubMed]
    [Google Scholar]
  23. Koboldt DC, Larson DE, Wilson RK. Using VarScan 2 for germline variant calling and somatic mutation detection. Curr Protoc Bioinformatics 2013; 44:11–17 [View Article][PubMed]
    [Google Scholar]
  24. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15 [View Article][PubMed]
    [Google Scholar]
  25. Stamatakis A. Using RAxML to infer phylogenies. Curr Protoc Bioinformatics 2015; 51:11–14 [View Article][PubMed]
    [Google Scholar]
  26. Page AJ, de Silva N, Hunt M, Quail MA, Parkhill J et al. Robust high-throughput prokaryote de novo assembly and improvement pipeline for Illumina data. Microb Genom 2016; 2:e000083 [View Article][PubMed]
    [Google Scholar]
  27. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article][PubMed]
    [Google Scholar]
  28. Carattoli A, Zankari E, García-Fernández A, Voldby Larsen M, Lund O et al. In silico detection and typing of plasmids using PlasmidFinder and plasmid multilocus sequence typing. Antimicrob Agents Chemother 2014; 58:3895–3903 [View Article][PubMed]
    [Google Scholar]
  29. Huang DW, Sherman BT, Tan Q, Collins JR, Alvord WG et al. The DAVID Gene Functional Classification Tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol 2007; 8:R183 [View Article][PubMed]
    [Google Scholar]
  30. Joensen KG, Scheutz F, Lund O, Hasman H, Kaas RS et al. Real-time whole-genome sequencing for routine typing, surveillance, and outbreak detection of verotoxigenic Escherichia coli . J Clin Microbiol 2014; 52:1501–1510 [View Article][PubMed]
    [Google Scholar]
  31. Brynildsrud O, Bohlin J, Scheffer L, Eldholm V. Rapid scoring of genes in microbial pan-genome-wide association studies with Scoary. Genome Biol 2016; 17:238 [View Article][PubMed]
    [Google Scholar]
  32. Hunt M, Mather AE, Sánchez-Busó L, Page AJ, Parkhill J et al. ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads. Microb Genom 2017; 3:e000131 [View Article][PubMed]
    [Google Scholar]
  33. Price LB, Johnson JR, Aziz M, Clabots C, Johnston B et al. The epidemic of extended-spectrum-β-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. mBio 2013; 4:e00377-13 [View Article][PubMed]
    [Google Scholar]
  34. Petty NK, Ben Zakour NL, Stanton-Cook M, Skippington E, Totsika M et al. Global dissemination of a multidrug resistant Escherichia coli clone. Proc Natl Acad Sci USA 2014; 111:5694–5699 [View Article][PubMed]
    [Google Scholar]
  35. Ben Zakour NL, Alsheikh-Hussain AS, Ashcroft MM, Khanh Nhu NT, Roberts LW et al. Sequential acquisition of virulence and fluoroquinolone resistance has shaped the evolution of Escherichia coli ST131. mBio 2016; 7:e0034700316 [View Article][PubMed]
    [Google Scholar]
  36. Tettelin H, Riley D, Cattuto C, Medini D. Comparative genomics: the bacterial pan-genome. Curr Opin Microbiol 2008; 11:472–477 [View Article][PubMed]
    [Google Scholar]
  37. Croucher NJ, Coupland PG, Stevenson AE, Callendrello A, Bentley SD et al. Diversification of bacterial genome content through distinct mechanisms over different timescales. Nat Commun 2014; 5:5471 [View Article][PubMed]
    [Google Scholar]
  38. Teufel R, Mascaraque V, Ismail W, Voss M, Perera J et al. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc Natl Acad Sci USA 2010; 107:14390–14395 [View Article][PubMed]
    [Google Scholar]
  39. Chen L, Zheng D, Liu B, Yang J, Jin Q. VFDB 2016: hierarchical and refined dataset for big data analysis - 10 years on. Nucleic Acids Res 2016; 44:D694–D697 [View Article][PubMed]
    [Google Scholar]
  40. Skyberg JA, Johnson TJ, Johnson JR, Clabots C, Logue CM et al. Acquisition of avian pathogenic Escherichia coli plasmids by a commensal E. coli isolate enhances its abilities to kill chicken embryos, grow in human urine, and colonize the murine kidney. Infect Immun 2006; 74:6287–6292 [View Article][PubMed]
    [Google Scholar]
  41. Tseng CC, Wu JJ, Liu HL, Sung JM, Huang JJ. Roles of host and bacterial virulence factors in the development of upper urinary tract infection caused by Escherichia coli . Am J Kidney Dis 2002; 39:744–752 [View Article][PubMed]
    [Google Scholar]
  42. Spaulding CN, Hultgren SJ. Adhesive pili in UTI pathogenesis and drug development. Pathogens 2016; 5:30 [View Article][PubMed]
    [Google Scholar]
  43. Wiles TJ, Kulesus RR, Mulvey MA. Origins and virulence mechanisms of uropathogenic Escherichia coli . Exp Mol Pathol 2008; 85:11–19 [View Article][PubMed]
    [Google Scholar]
  44. Dautin N. Serine protease autotransporters of enterobacteriaceae (SPATEs): biogenesis and function. Toxins 2010; 2:1179–1206 [View Article][PubMed]
    [Google Scholar]
  45. Ren CP, Chaudhuri RR, Fivian A, Bailey CM, Antonio M et al. The ETT2 gene cluster, encoding a second type III secretion system from Escherichia coli, is present in the majority of strains but has undergone widespread mutational attrition. J Bacteriol 2004; 186:3547–3560 [View Article][PubMed]
    [Google Scholar]
  46. Ristow LC, Welch RA. Hemolysin of uropathogenic Escherichia coli: a cloak or a dagger?. Biochim Biophys Acta 2016; 1858:538–545 [View Article][PubMed]
    [Google Scholar]
  47. Page R, Peti W. Toxin-antitoxin systems in bacterial growth arrest and persistence. Nat Chem Biol 2016; 12:208–214 [View Article][PubMed]
    [Google Scholar]
  48. Zhang Y, Zhu L, Zhang J, Inouye M. Characterization of ChpBK, an mRNA interferase from Escherichia coli . J Biol Chem 2005; 280:26080–26088 [View Article][PubMed]
    [Google Scholar]
  49. Maisonneuve E, Shakespeare LJ, Jørgensen MG, Gerdes K. Bacterial persistence by RNA endonucleases. Proc Natl Acad Sci USA 2011; 108:13206–13211 [View Article][PubMed]
    [Google Scholar]
  50. Andersen C, Rak B, Benz R. The gene bglH present in the bgl operon of Escherichia coli, responsible for uptake and fermentation of beta-glucosides encodes for a carbohydrate-specific outer membrane porin. Mol Microbiol 1999; 31:499–510 [View Article][PubMed]
    [Google Scholar]
  51. Christensen-Dalsgaard M, Jørgensen MG, Gerdes K. Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses. Mol Microbiol 2010; 75:333–348 [View Article][PubMed]
    [Google Scholar]
  52. Cambray G, Guerout AM, Mazel D. Integrons. Annu Rev Genet 2010; 44:141–166 [View Article][PubMed]
    [Google Scholar]
  53. Mathers AJ, Peirano G, Pitout JD. The role of epidemic resistance plasmids and international high-risk clones in the spread of multidrug-resistant Enterobacteriaceae. Clin Microbiol Rev 2015; 28:565–591 [View Article][PubMed]
    [Google Scholar]
  54. Bajaj P, Singh NS, Virdi JS. Escherichia coli β-lactamases: what really matters. Front Microbiol 2016; 7:417 [View Article][PubMed]
    [Google Scholar]
  55. Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updat 2010; 13:151–171 [View Article][PubMed]
    [Google Scholar]
  56. Gestal AM, Stokes HW, Partridge SR, Hall RM. Recombination between the dfrA12-orfF-aadA2 cassette array and an aadA1 gene cassette creates a hybrid cassette, aadA8b. Antimicrob Agents Chemother 2005; 49:4771–4774 [View Article][PubMed]
    [Google Scholar]
  57. Shimada T, Yamamoto K, Ishihama A. Involvement of the leucine response transcription factor LeuO in regulation of the genes for sulfa drug efflux. J Bacteriol 2009; 191:4562–4571 [View Article][PubMed]
    [Google Scholar]
  58. Picard B, Garcia JS, Gouriou S, Duriez P, Brahimi N et al. The link between phylogeny and virulence in Escherichia coli extraintestinal infection. Infect Immun 1999; 67:546–553[PubMed]
    [Google Scholar]
  59. Wirth T, Falush D, Lan R, Colles F, Mensa P et al. Sex and virulence in Escherichia coli: an evolutionary perspective. Mol Microbiol 2006; 60:1136–1151 [View Article][PubMed]
    [Google Scholar]
  60. Maurelli AT. Black holes, antivirulence genes, and gene inactivation in the evolution of bacterial pathogens. FEMS Microbiol Lett 2007; 267:1–8 [View Article][PubMed]
    [Google Scholar]
  61. Jørgensen SB, Søraas A, Sundsfjord A, Liestøl K, Leegaard TM et al. Fecal carriage of extended spectrum β-lactamase producing Escherichia coli and Klebsiella pneumoniae after urinary tract infection - a three year prospective cohort study. PLoS One 2017; 12:e0173510 [View Article][PubMed]
    [Google Scholar]
  62. Lewis K. Persister cells. Annu Rev Microbiol 2010; 64:357–372 [View Article][PubMed]
    [Google Scholar]
  63. Levin-Reisman I, Ronin I, Gefen O, Braniss I, Shoresh N et al. Antibiotic tolerance facilitates the evolution of resistance. Science 2017; 355:826–830 [View Article][PubMed]
    [Google Scholar]
  64. Ho BT, Dong TG, Mekalanos JJ. A view to a kill: the bacterial type VI secretion system. Cell Host Microbe 2014; 15:9–21 [View Article][PubMed]
    [Google Scholar]
  65. Coque TM, Novais A, Carattoli A, Poirel L, Pitout J et al. Dissemination of clonally related Escherichia coli strains expressing extended-spectrum β-lactamase CTX-M-15. Emerg Infect Dis 2008; 14:195–200 [View Article][PubMed]
    [Google Scholar]
  66. Cantón R, González-Alba JM, Galán JC. CTX-M enzymes: origin and diffusion. Front Microbiol 2012; 3:110 [View Article][PubMed]
    [Google Scholar]
  67. Laupland KB, Gregson DB, Church DL, Ross T, Pitout JD. Incidence, risk factors and outcomes of Escherichia coli bloodstream infections in a large Canadian region. Clin Microbiol Infect 2008; 14:1041–1047 [View Article][PubMed]
    [Google Scholar]
  68. Lefort A, Panhard X, Clermont O, Woerther PL, Branger C et al. Host factors and portal of entry outweigh bacterial determinants to predict the severity of Escherichia coli bacteremia. J Clin Microbiol 2011; 49:777–783 [View Article][PubMed]
    [Google Scholar]
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