1887

Abstract

Helicobacter cinaedi is an emerging pathogen causing bacteraemia and cellulitis. Nosocomial transmission of this microbe has been described, but detailed molecular-epidemiological analyses have not been performed. Here, we describe the results of a multi-step genome-wide phylogenetic analysis of a suspected intra-hospital outbreak of H. cinaedi that occurred in a hospital in Japan. The outbreak was recognized by the infectious control team (ICT) of the hospital as a sudden increase in H. cinaedi bacteraemia. ICT defined this outbreak case based on 16S rRNA sequence data and epidemiological information, but were unable to determine the source and route of the infections. We therefore re-investigated this case using whole-genome sequencing (WGS). We first performed a species-wide analysis using publicly available genome sequences to understand the level of genomic diversity of this under-studied species. The clusters identified were then separately analysed using the genome sequence of a representative strain in each cluster as a reference. These analyses provided a high-level phylogenetic resolution of each cluster, identified a confident set of outbreak isolates, and discriminated them from other closely related but distinct clones, which were locally circulating and invaded the hospital during the same period. By considering the epidemiological data, possible strain transmission chains were inferred, which highlighted the role of asymptomatic carriers or environmental contamination. The emergence of a subclone with increased resistance to fluoroquinolones in the outbreak was also recognized. Our results demonstrate the impact of the use of a closely related genome as a reference to maximize the power of WGS.

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2019-01-17
2019-09-17
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References

  1. Solnick JV, Schauer DB. Emergence of diverse Helicobacter species in the pathogenesis of gastric and enterohepatic diseases. Clin Microbiol Rev 2001;14:59–97 [CrossRef][PubMed]
    [Google Scholar]
  2. Kawamura Y, Tomida J, Morita Y, Fujii S, Okamoto T et al. Clinical and bacteriological characteristics of Helicobacter cinaedi infection. J Infect Chemother 2014;20:517–526 [CrossRef][PubMed]
    [Google Scholar]
  3. Totten PA, Fennell CL, Tenover FC, Wezenberg JM, Perine PL et al. Campylobacter cinaedi (sp. nov.) and Campylobacter fennelliae (sp. nov.): two new Campylobacter species associated with enteric disease in homosexual men. J Infect Dis 1985;151:131–139 [CrossRef][PubMed]
    [Google Scholar]
  4. Lasry S, Simon J, Marais A, Pouchot J, Vinceneux P et al. Helicobacter cinaedi septic arthritis and bacteremia in an immunocompetent patient. Clin Infect Dis 2000;31:201–202 [CrossRef][PubMed]
    [Google Scholar]
  5. Kitamura T, Kawamura Y, Ohkusu K, Masaki T, Iwashita H et al. Helicobacter cinaedi cellulitis and bacteremia in immunocompetent hosts after orthopedic surgery. J Clin Microbiol 2007;45:31–38 [CrossRef][PubMed]
    [Google Scholar]
  6. Holst H, Andresen K, Blom J, Højlyng N, Kemp M et al. A case of Helicobacter cinaedi bacteraemia in a previously healthy person with cellulitis. Open Microbiol J 2008;2:29–31 [CrossRef][PubMed]
    [Google Scholar]
  7. Shimizu Y, Gomi H, Ishioka H, Isono M. Refractory to treat Helicobacter cinaedi bacteremia with bilateral lower extremities cellulitis in an immunocompetent patient. IDCases 2016;5:9–11 [CrossRef][PubMed]
    [Google Scholar]
  8. Burman WJ, Cohn DL, Reves RR, Wilson ML. Multifocal cellulitis and monoarticular arthritis as manifestations of Helicobacter cinaedi bacteremia. Clin Infect Dis 1995;20:564–570 [CrossRef][PubMed]
    [Google Scholar]
  9. Kiehlbauch JA, Brenner DJ, Cameron DN, Steigerwalt AG, Makowski JM et al. Genotypic and phenotypic characterization of Helicobacter cinaedi and Helicobacter fennelliae strains isolated from humans and animals. J Clin Microbiol 1995;33:2940–2947[PubMed]
    [Google Scholar]
  10. Fox JG, Handt L, Sheppard BJ, Xu S, Dewhirst FE et al. Isolation of Helicobacter cinaedi from the colon, liver, and mesenteric lymph node of a rhesus monkey with chronic colitis and hepatitis. J Clin Microbiol 2001;39:1580–1585 [CrossRef][PubMed]
    [Google Scholar]
  11. Orlicek SL, Welch DF, Kuhls TL. Septicemia and meningitis caused by Helicobacter cinaedi in a neonate. J Clin Microbiol 1993;31:569–571[PubMed]
    [Google Scholar]
  12. Araoka H, Baba M, Okada C, Kimura M, Sato T et al. First evidence of bacterial translocation from the intestinal tract as a route of Helicobacter cinaedi bacteremia. Helicobacter 2018;23:e12458 [CrossRef][PubMed]
    [Google Scholar]
  13. Araoka H, Baba M, Okada C, Kimura M, Sato T et al. Risk factors for recurrent Helicobacter cinaedi bacteremia and the efficacy of selective digestive decontamination with kanamycin to prevent recurrence. Clin Infect Dis 2018;67:573–578 [CrossRef][PubMed]
    [Google Scholar]
  14. Oyama K, Khan S, Okamoto T, Fujii S, Ono K et al. Identification of and screening for human Helicobacter cinaedi infections and carriers via nested PCR. J Clin Microbiol 2012;50:3893–3900 [CrossRef][PubMed]
    [Google Scholar]
  15. Araoka H, Baba M, Kimura M, Abe M, Inagawa H et al. Clinical characteristics of bacteremia caused by Helicobacter cinaedi and time required for blood cultures to become positive. J Clin Microbiol 2014;52:1519–1522 [CrossRef][PubMed]
    [Google Scholar]
  16. Matsumoto T, Goto M, Murakami H, Tanaka T, Nishiyama H et al. Multicenter study to evaluate bloodstream infection by Helicobacter cinaedi in Japan. J Clin Microbiol 2007;45:2853–2857 [CrossRef][PubMed]
    [Google Scholar]
  17. Shimizu S, Shimizu H. Cutaneous manifestations of Helicobacter cinaedi: a review. Br J Dermatol 2016;175:62–68 [CrossRef][PubMed]
    [Google Scholar]
  18. Bateman AC, Butler-Wu SM. The brief case: bacteremia caused by Helicobacter cinaedi. J Clin Microbiol 2017;55:5–9 [CrossRef][PubMed]
    [Google Scholar]
  19. Uçkay I, Garbino J, Dietrich PY, Ninet B, Rohner P et al. Recurrent bacteremia with Helicobacter cinaedi: case report and review of the literature. BMC Infect Dis 2006;6:86 [CrossRef][PubMed]
    [Google Scholar]
  20. Minauchi K, Takahashi S, Sakai T, Kondo M, Shibayama K et al. The nosocomial transmission of Helicobacter cinaedi infections in immunocompromised patients. Intern Med 2010;49:1733–1739 [CrossRef][PubMed]
    [Google Scholar]
  21. Rimbara E, Mori S, Matsui M, Suzuki S, Wachino J et al. Molecular epidemiologic analysis and antimicrobial resistance of Helicobacter cinaedi isolated from seven hospitals in Japan. J Clin Microbiol 2012;50:2553–2560 [CrossRef][PubMed]
    [Google Scholar]
  22. Rimbara E, Mori S, Kim H, Matsui M, Suzuki S et al. Helicobacter cinaedi and Helicobacter fennelliae transmission in a hospital from 2008 to 2012. J Clin Microbiol 2013;51:2439–2442 [CrossRef][PubMed]
    [Google Scholar]
  23. Köser CU, Holden MT, Ellington MJ, Cartwright EJ, Brown NM et al. Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N Engl J Med 2012;366:2267–2275 [CrossRef][PubMed]
    [Google Scholar]
  24. Tong SY, Holden MT, Nickerson EK, Cooper BS, Köser CU et al. Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting. Genome Res 2015;25:111–118 [CrossRef][PubMed]
    [Google Scholar]
  25. Snitkin ES, Zelazny AM, Thomas PJ, Stock F, Henderson DK et al. Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing. Sci Transl Med 2012;4:148ra116 [CrossRef][PubMed]
    [Google Scholar]
  26. Jia H, Du P, Yang H, Zhang Y, Wang J et al. Nosocomial transmission of Clostridium difficile ribotype 027 in a Chinese hospital, 2012-2014, traced by whole genome sequencing. BMC Genomics 2016;17:405 [CrossRef][PubMed]
    [Google Scholar]
  27. Moradigaravand D, Gouliouris T, Blane B, Naydenova P, Ludden C et al. Within-host evolution of Enterococcus faecium during longitudinal carriage and transition to bloodstream infection in immunocompromised patients. Genome Med 2017;9:119 [CrossRef][PubMed]
    [Google Scholar]
  28. Perrin A, Larsonneur E, Nicholson AC, Edwards DJ, Gundlach KM et al. Evolutionary dynamics and genomic features of the Elizabethkingia anophelis 2015 to 2016 Wisconsin outbreak strain. Nat Commun 2017;8:15483 [CrossRef][PubMed]
    [Google Scholar]
  29. Goto T, Ogura Y, Hirakawa H, Tomida J, Morita Y et al. Complete genome sequence of Helicobacter cinaedi strain PAGU611, isolated in a case of human bacteremia. J Bacteriol 2012;194:3744–3745 [CrossRef][PubMed]
    [Google Scholar]
  30. Miyoshi-Akiyama T, Takeshita N, Ohmagari N, Kirikae T. Complete genome sequence of Helicobacter cinaedi type strain ATCC BAA-847. J Bacteriol 2012;194:5692 [CrossRef][PubMed]
    [Google Scholar]
  31. Rimbara E, Mori S, Kim H, Suzuki M, Shibayama K. Mutations in genes encoding penicillin-binding proteins and efflux pumps play a role in β-lactam resistance in Helicobacter cinaedi. Antimicrob Agents Chemother 2018;62::e02036-17 [CrossRef][PubMed]
    [Google Scholar]
  32. Tomida J, Morita Y, Shibayama K, Kikuchi K, Sawa T et al. Diversity and microevolution of CRISPR loci in Helicobacter cinaedi. PLoS One 2017;12:e0186241 [CrossRef][PubMed]
    [Google Scholar]
  33. Tomida J, Oumi A, Okamoto T, Morita Y, Okayama A et al. Comparative evaluation of agar dilution and broth microdilution methods for antibiotic susceptibility testing of Helicobacter cinaedi. Microbiol Immunol 2013;57:353–358 [CrossRef][PubMed]
    [Google Scholar]
  34. Kajitani R, Toshimoto K, Noguchi H, Toyoda A, Ogura Y et al. Efficient de novo assembly of highly heterozygous genomes from whole-genome shotgun short reads. Genome Res 2014;24:1384–1395 [CrossRef][PubMed]
    [Google Scholar]
  35. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014;30:2068–2069 [CrossRef][PubMed]
    [Google Scholar]
  36. Kurtz S, Phillippy A, Delcher AL, Smoot M, Shumway M et al. Versatile and open software for comparing large genomes. Genome Biol 2004;5:R12 [CrossRef][PubMed]
    [Google Scholar]
  37. 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]
  38. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014;30:1312–1313 [CrossRef][PubMed]
    [Google Scholar]
  39. Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 2016;33:1870–1874 [CrossRef][PubMed]
    [Google Scholar]
  40. Rambaut A, Lam TT, Max Carvalho L, Pybus OG. Exploring the temporal structure of heterochronous sequences using TempEst (formerly Path-O-Gen). Virus Evol 2016;2:vew007 [CrossRef][PubMed]
    [Google Scholar]
  41. Ruiz J. Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection. J Antimicrob Chemother 2003;51:1109–1117 [CrossRef][PubMed]
    [Google Scholar]
  42. Young BC, Golubchik T, Batty EM, Fung R, Larner-Svensson H et al. Evolutionary dynamics of Staphylococcus aureus during progression from carriage to disease. Proc Natl Acad Sci USA 2012;109:4550–4555 [CrossRef][PubMed]
    [Google Scholar]
  43. Didelot X, Nell S, Yang I, Woltemate S, van der Merwe S et al. Genomic evolution and transmission of Helicobacter pylori in two South African families. Proc Natl Acad Sci USA 2013;110:13880–13885 [CrossRef][PubMed]
    [Google Scholar]
  44. Stoesser N, Sheppard AE, Moore CE, Golubchik T, Parry CM et al. Extensive within-host diversity in fecally carried extended-spectrum-β-lactamase-producing Escherichia coli isolates: implications for transmission analyses. J Clin Microbiol 2015;53:2122–2131 [CrossRef][PubMed]
    [Google Scholar]
  45. Gorrie CL, Mirceta M, Wick RR, Judd LM, Wyres KL et al. Antimicrobial-resistant Klebsiella pneumoniae carriage and infection in specialized geriatric care wards linked to acquisition in the referring hospital. Clin Infect Dis 2018;67:161–170 [CrossRef][PubMed]
    [Google Scholar]
  46. Kong LY, Eyre DW, Corbeil J, Raymond F, Walker AS et al. Clostridium difficile: Investigating Transmission Patterns between Infected and Colonized Patients using whole Genome Sequencing. Clin Infect Dis 2018; ciy457 [CrossRef][PubMed]
    [Google Scholar]
  47. Harrison EM, Ludden C, Brodrick HJ, Blane B, Brennan G et al. Transmission of methicillin-resistant Staphylococcus aureus in long-term care facilities and their related healthcare networks. Genome Med 2016;8:102 [CrossRef][PubMed]
    [Google Scholar]
  48. Fennell CL, Totten PA, Quinn TC, Patton DL, Holmes KK et al. Characterization of Campylobacter-like organisms isolated from homosexual men. J Infect Dis 1984;149:58–66 [CrossRef][PubMed]
    [Google Scholar]
  49. Vandamme P, Falsen E, Pot B, Kersters K, de Ley J. Identification of Campylobacter cinaedi isolated from blood and feces of children and adult females. J Clin Microbiol 1990;28:1016–1020[PubMed]
    [Google Scholar]
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