1887

Abstract

Sexually transmissible enteric infections (STEIs) are commonly associated with transmission among men who have sex with men (MSM). In the past decade, the UK has experienced multiple parallel STEI emergences in MSM caused by a range of bacterial species of the genus Shigella, and an outbreak of an uncommon serotype (O117 : H7) of Shiga-toxin-producing Escherichia coli (STEC). Here, we used microbial genomics on 6 outbreak and 30 sporadic STEC O117 : H7 isolates to explore the origins and pathogenic drivers of the STEC O117 : H7 emergence in MSM. Using genomic epidemiology, we found that the STEC O117 : H7 outbreak lineage was potentially imported from Latin America and likely continues to circulate both in the UK MSM population and in Latin America. We found genomic relationships consistent with existing symptomatic evidence for chronic infection with this STEC serotype. Comparative genomic analysis indicated the existence of a novel Shiga toxin 1-encoding prophage in the outbreak isolates, and evidence of horizontal gene exchange among the STEC O117 : H7 outbreak lineage and other enteric pathogens. There was no evidence of increased virulence in the outbreak strains relative to contextual isolates, but the outbreak lineage was associated with azithromycin resistance. Comparing these findings with similar genomic investigations of emerging MSM-associated Shigella in the UK highlighted many parallels, the most striking of which was the importance of the azithromycin phenotype for STEI emergence in this patient group.

Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000181
2018-05-21
2019-08-24
Loading full text...

Full text loading...

/deliver/fulltext/mgen/4/7/mgen000181.html?itemId=/content/journal/mgen/10.1099/mgen.0.000181&mimeType=html&fmt=ahah

References

  1. de Vries HJ, Zingoni A, White JA, Ross JD, Kreuter A. 2013 European guideline on the management of proctitis, proctocolitis and enteritis caused by sexually transmissible pathogens. Int J STD AIDS 2014;25:465–474 [CrossRef][PubMed]
    [Google Scholar]
  2. Hughes G, Field N. The epidemiology of sexually transmitted infections in the UK: impact of behavior, services and interventions. Future Microbiol 2015;10:35–51 [CrossRef][PubMed]
    [Google Scholar]
  3. Simms I, Field N, Jenkins C, Childs T, Gilbart VL et al. Intensified shigellosis epidemic associated with sexual transmission in men who have sex with men–Shigella flexneri and S. sonnei in England, 2004 to end of February 2015. Euro Surveill 2015;20:21097 [CrossRef][PubMed]
    [Google Scholar]
  4. Baker KS, Dallman TJ, Ashton PM, Day M, Hughes G et al. Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study. Lancet Infect Dis 2015;15:913–921 [CrossRef][PubMed]
    [Google Scholar]
  5. Baker KS, Dallman TJ, Field N, Childs T, Were J et al. Common determinants of antimicrobial resistance in sequential episodes of sexually transmitted shigellosis in men who have sex with men: a cross-sectional study. The Lancet 2017;389:S24 [CrossRef]
    [Google Scholar]
  6. Baker KS, Dallman TJ, Field N, Childs T, Mitchell H et al. Horizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species. Nat Commun 2018;9:1462 [CrossRef][PubMed]
    [Google Scholar]
  7. Simms I, Gilbart VL, Byrne L, Jenkins C, Adak GK et al. Identification of verocytotoxin-producing Escherichia coli O117:H7 in men who have sex with men, England, November 2013 to August 2014. Euro Surveill 2014;19:20946 [CrossRef][PubMed]
    [Google Scholar]
  8. Hunt JM. Shiga toxin-producing Escherichia coli (STEC). Clin Lab Med 2010;30:21–45 [CrossRef][PubMed]
    [Google Scholar]
  9. Ethelberg S, Olsen KE, Scheutz F, Jensen C, Schiellerup P et al. Virulence factors for hemolytic uremic syndrome, Denmark. Emerg Infect Dis 2004;10:842–847 [CrossRef][PubMed]
    [Google Scholar]
  10. Dallman T, Cross L, Bishop C, Perry N, Olesen B et al. Whole genome sequencing of an unusual serotype of Shiga toxin-producing Escherichia coli. Emerg Infect Dis 2013;19:1302–1304 [CrossRef][PubMed]
    [Google Scholar]
  11. Olesen B, Jensen C, Olsen K, Fussing V, Gerner-Smidt P et al. VTEC O117:K1:H7. A new clonal group of E. coli associated with persistent diarrhoea in Danish travellers. Scand J Infect Dis 2005;37:288–294 [CrossRef][PubMed]
    [Google Scholar]
  12. Gilbart VL, Simms I, Jenkins C, Furegato M, Gobin M et al. Sex, drugs and smart phone applications: findings from semistructured interviews with men who have sex with men diagnosed with Shigella flexneri 3a in England and Wales. Sex Transm Infect 2015;91:598–602 [CrossRef][PubMed]
    [Google Scholar]
  13. Chattaway MA, Dallman TJ, Gentle A, Wright MJ, Long SE et al. Whole genome sequencing for public health surveillance of Shiga toxin-producing Escherichia coli other than serogroup O157. Front Microbiol 2016;7:258 [CrossRef][PubMed]
    [Google Scholar]
  14. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012;19:455–477 [CrossRef][PubMed]
    [Google Scholar]
  15. 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 [CrossRef][PubMed]
    [Google Scholar]
  16. Boetzer M, Henkel CV, Jansen HJ, Butler D, Pirovano W. Scaffolding pre-assembled contigs using SSPACE. Bioinformatics 2011;27:578–579 [CrossRef][PubMed]
    [Google Scholar]
  17. Boetzer M, Pirovano W. Toward almost closed genomes with GapFiller. Genome Biol 2012;13:R56 [CrossRef][PubMed]
    [Google Scholar]
  18. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014;30:2068–2069 [CrossRef][PubMed]
    [Google Scholar]
  19. Chin CS, Alexander DH, Marks P, Klammer AA, Drake J et al. Nonhybrid, finished microbial genome assemblies from long-read SMRT sequencing data. Nat Methods 2013;10:563–569 [CrossRef][PubMed]
    [Google Scholar]
  20. Hunt M, Silva ND, Otto TD, Parkhill J, Keane JA et al. Circlator: automated circularization of genome assemblies using long sequencing reads. Genome Biol 2015;16:294 [CrossRef][PubMed]
    [Google Scholar]
  21. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The sequence alignment/map format and SAMtools. Bioinformatics 2009;25:2078–2079 [CrossRef][PubMed]
    [Google Scholar]
  22. 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 [CrossRef][PubMed]
    [Google Scholar]
  23. Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2016;2:e000056 [CrossRef][PubMed]
    [Google Scholar]
  24. Stamatakis A. RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 2006;22:2688–2690 [CrossRef][PubMed]
    [Google Scholar]
  25. Letunic I, Bork P. Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res 2016;44:W242–W245 [CrossRef][PubMed]
    [Google Scholar]
  26. Zhou Y, Liang Y, Lynch KH, Dennis JJ, Wishart DS. PHAST: a fast phage search tool. Nucleic Acids Res 2011;39:W347–W352 [CrossRef][PubMed]
    [Google Scholar]
  27. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990;215:403–410 [CrossRef][PubMed]
    [Google Scholar]
  28. Rice P, Longden I, Bleasby A. EMBOSS: the European molecular biology open software suite. Trends Genet 2000;16:276–277 [CrossRef][PubMed]
    [Google Scholar]
  29. Zankari E, Hasman H, Cosentino S, Vestergaard M, Rasmussen S et al. Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother 2012;67:2640–2644 [CrossRef][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 [CrossRef][PubMed]
    [Google Scholar]
  31. Alikhan NF, Petty NK, Ben Zakour NL, Beatson SA. BLAST ring image generator (BRIG): simple prokaryote genome comparisons. BMC Genomics 2011;12:402 [CrossRef][PubMed]
    [Google Scholar]
  32. Yang F, Yang J, Zhang X, Chen L, Jiang Y et al. Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery. Nucleic Acids Res 2005;33:6445–6458 [CrossRef][PubMed]
    [Google Scholar]
  33. Ahmed SA, Awosika J, Baldwin C, Bishop-Lilly KA, Biswas B et al. Genomic comparison of Escherichia coli O104:H4 isolates from 2009 and 2011 reveals plasmid, and prophage heterogeneity, including Shiga toxin encoding phage stx2. PLoS One 2012;7:e48228 [CrossRef][PubMed]
    [Google Scholar]
  34. Künne C, Billion A, Mshana SE, Schmiedel J, Domann E et al. Complete sequences of plasmids from the hemolytic-uremic syndrome-associated Escherichia coli strain HUSEC41. J Bacteriol 2012;194:532–533 [CrossRef][PubMed]
    [Google Scholar]
  35. Kyriakidis DA, Tiligada E. Signal transduction and adaptive regulation through bacterial two-component systems: the Escherichia coli AtoSC paradigm. Amino Acids 2009;37:443–458 [CrossRef][PubMed]
    [Google Scholar]
  36. Reidl S, Lehmann A, Schiller R, Salam Khan A, Dobrindt U. Impact of O-glycosylation on the molecular and cellular adhesion properties of the Escherichia coli autotransporter protein Ag43. Int J Med Microbiol 2009;299:389–401 [CrossRef][PubMed]
    [Google Scholar]
  37. Carter CC, Fierer J, Chiu WW, Looney DJ, Strain M et al. A novel Shiga toxin 1a-converting bacteriophage of Shigella sonnei with close relationship to Shiga toxin 2-converting pages of Escherichia coli. Open Forum Infect Dis 2016;3:ofw079 [CrossRef][PubMed]
    [Google Scholar]
  38. Adriaenssens E, Brister JR. How to name and classify your phage: an informal guide. Viruses 2017;9:70 [CrossRef][PubMed]
    [Google Scholar]
  39. Bowen A, Grass J, Bicknese A, Campbell D, Hurd J et al. Elevated risk for antimicrobial drug-resistant shigella infection among men who have sex with men, United States, 2011–2015. Emerg Infect Dis 2016;22:1613–1616 [CrossRef][PubMed]
    [Google Scholar]
  40. Bagel S, Hüllen V, Wiedemann B, Heisig P. Impact of gyrA and parC mutations on quinolone resistance, doubling time, and supercoiling degree of Escherichia coli. Antimicrob Agents Chemother 1999;43:868–875[PubMed]
    [Google Scholar]
  41. Montero DA, Velasco J, del Canto F, Puente JL, Padola NL et al. Locus of adhesion and autoaggregation (LAA), a pathogenicity island present in emerging Shiga toxin-producing Escherichia coli strains. Sci Rep 2017;7:7011 [CrossRef][PubMed]
    [Google Scholar]
  42. Michelacci V, Tozzoli R, Caprioli A, Martínez R, Scheutz F et al. A new pathogenicity island carrying an allelic variant of the subtilase cytotoxin is common among Shiga toxin producing Escherichia coli of human and ovine origin. Clin Microbiol Infect 2013;19:E149E156 [CrossRef][PubMed]
    [Google Scholar]
  43. Murray K, Reddy V, Kornblum JS, Waechter H, Chicaiza LF et al. Increasing antibiotic resistance in Shigella spp. from infected New York city residents, New York, USA. Emerg Infect Dis 2017;23:332–335 [CrossRef][PubMed]
    [Google Scholar]
  44. Ahmed N, Chung E, Morris-Jones S, Miller RF. Correspondence to invasive shigellosis in MSM. Int J STD AIDS 2017;28:421–422 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000181
Loading
/content/journal/mgen/10.1099/mgen.0.000181
Loading

Data & Media loading...

Supplementary File 1

PDF

Supplementary File 2

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error