1887

Abstract

Antimicrobial-resistance (AMR) genes can be transferred between microbial cells via horizontal gene transfer (HGT), which involves mobile and integrative elements such as plasmids, bacteriophages, transposons, integrons and pathogenicity islands. Bacteriophages are found in abundance in the microbial world, but their role in virulence and AMR has not fully been elucidated in the . With short-read sequencing paving the way to systematic high-throughput AMR gene detection, long-read sequencing technologies now enable us to establish how such genes are structurally connected into meaningful genomic units, raising questions about how they might cooperate to achieve their biological function. Here, we describe a novel ~98 kbp circular P1-bacteriophage-like plasmid termed ph681355 isolated from a clinical serovar Typhi isolate. It carries , an IncY plasmid replicon ( gene) and the IS mobile element and is, to our knowledge, the first reported P1-bacteriophage-like plasmid (phage-plasmid) in . Typhi. We compared ph681355 to two previously described phage-plasmids, pSJ46 from . serovar Indiana and pMCR-1-P3 from , and found high nucleotide similarity across the backbone. However, we saw low ph681355 backbone similarity to plasmid p60006 associated with the extensively drug-resistant . Typhi outbreak isolate in Pakistan, providing evidence of an alternative route for transmission. Our discovery highlights the importance of utilizing long-read sequencing in interrogating bacterial genomic architecture to fully understand AMR mechanisms and their clinical relevance. It also raises questions regarding how widespread bacteriophage-mediated HGT might be, suggesting that the resulting genomic plasticity might be higher than previously thought.

Funding
This study was supported by the:
  • Biotechnology and Biological Sciences Research Council (Award BB/R012504/1 and BBS/E/F/000PR10348)
    • Principle Award Recipient: EmmaV Waters
  • Biotechnology and Biological Sciences Research Council (Award BB/R012504/1 and BBS/E/F/000PR10348)
    • Principle Award Recipient: GemmaC Langridge
  • National Institute for Health Research Health Protection Research Unit
    • Principle Award Recipient: MatthewT Bird
  • National Institute for Health Research Health Protection Research Unit (Award NIHR200892)
    • Principle Award Recipient: PaoloRibeca
  • National Institute for Health Research Health Protection Research Unit (Award NIHR200892)
    • Principle Award Recipient: MarieAnne Chattaway
  • National Institute for Health Research Health Protection Research Unit (Award NIHR200892)
    • Principle Award Recipient: ClaireJenkins
  • National Institute for Health Research Health Protection Research Unit (Award NIHR200892)
    • Principle Award Recipient: DavidR Greig
  • This information is licensed under the Open Government Licence 3.0. This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-12-05
2024-03-29
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References

  1. Stanaway JD, Reiner RC, Blacker BF, Goldberg EM, Khalil IA et al. The global burden of typhoid and paratyphoid fevers: a systematic analysis for the global burden of disease study 2017. Lancet Infect Dis 2019; 19:369–381 [View Article] [PubMed]
    [Google Scholar]
  2. Klemm EJ, Shakoor S, Page AJ, Qamar FN, Judge K et al. Emergence of an extensively drug-resistant Salmonella enterica serovar Typhi clone harboring a promiscuous plasmid encoding resistance to fluoroquinolones and third-generation cephalosporins. mBio 2018; 9:e00105-18 [View Article]
    [Google Scholar]
  3. Nair S, Chattaway M, Langridge GC, Gentle A, Day M et al. ESBL-producing strains isolated from imported cases of enteric fever in England and Wales reveal multiple chromosomal integrations of blaCTX-M-15 in XDR Salmonella Typhi. J Antimicrob Chemother 2021; 76:1459–1466 [View Article] [PubMed]
    [Google Scholar]
  4. Godbole GS, Day MR, Murthy S, Chattaway MA, Nair S. First report of CTX-M-15 Salmonella Typhi from England. Clin Infect Dis 2018; 66:1976–1977 [View Article]
    [Google Scholar]
  5. Nizamuddin S, Ching C, Kamal R, Zaman MH, Sultan F. Continued outbreak of ceftriaxone-resistant Salmonella enterica serotype Typhi across Pakistan and assessment of knowledge and practices among healthcare workers. Am J Trop Med Hyg 2021; 104:1265–1270 [View Article] [PubMed]
    [Google Scholar]
  6. Qureshi S, Naveed AB, Yousafzai MT, Ahmad K, Ansari S et al. Response of extensively drug resistant Salmonella Typhi to treatment with meropenem and azithromycin, in Pakistan. PLoS Negl Trop Dis 2020; 14:e0008682 [View Article] [PubMed]
    [Google Scholar]
  7. Herdman MT, Karo B, Dave J, Katwa P, Freedman J et al. Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014–2019: a cross-sectional analytical study. J Med Microbiol 2021; 70:001359 [View Article]
    [Google Scholar]
  8. CDC Extensively Drug-Resistant Salmonella Typhi Infections among U.S. Residents without International Travel, CDC Health Advisory, CDCHAN-00439 ( https://emergency.CDC.gov/han/2021/han00439.asp) Atlanta, GA: Centers for Disease Control and Prevention; 2021
    [Google Scholar]
  9. Cantón R, González-Alba JM, Galán JC. CTX-M enzymes: origin and diffusion. Front Microbiol 2012; 3:110 [View Article] [PubMed]
    [Google Scholar]
  10. Aviv G, Tsyba K, Steck N, Salmon-Divon M, Cornelius A et al. A unique megaplasmid contributes to stress tolerance and pathogenicity of an emergent Salmonella enterica serovar Infantis strain. Environ Microbiol 2014; 16:977–994 [View Article] [PubMed]
    [Google Scholar]
  11. Goh S, Hussain H, Chang BJ, Emmett W, Riley TV et al. Phage ϕC2 mediates transduction of Tn6215, encoding erythromycin resistance, between Clostridium difficile strains. mBio 2013; 4:e00840-13 [View Article] [PubMed]
    [Google Scholar]
  12. Hyder SL, Streitfeld MM. Transfer of erythromycin resistance from clinically isolated lysogenic strains of Streptococcus pyogenes via their endogenous phage. J Infect Dis 1978; 138:281–286 [View Article] [PubMed]
    [Google Scholar]
  13. Billard-Pomares T, Fouteau S, Jacquet ME, Roche D, Barbe V et al. Characterization of a P1-like bacteriophage carrying an SHV-2 extended-spectrum β-lactamase from an Escherichia coli strain. Antimicrob Agents Chemother 2014; 58:6550–6557 [View Article] [PubMed]
    [Google Scholar]
  14. Yang L, Li W, Jiang G-Z, Zhang W-H, Ding H-Z et al. Characterization of a P1-like bacteriophage carrying CTX-M-27 in Salmonella spp. resistant to third generation cephalosporins isolated from pork in China. Sci Rep 2017; 7:40710 [View Article] [PubMed]
    [Google Scholar]
  15. Zhang C, Feng Y, Liu F, Jiang H, Qu Z et al. A phage-like IncY plasmid carrying the mcr-1 gene in Escherichia coli from a pig farm in China. Antimicrob Agents Chemother 2017; 61:e02035-16 [View Article] [PubMed]
    [Google Scholar]
  16. Wahl A, Battesti A, Ansaldi M. Prophages in Salmonella enterica: a driving force in reshaping the genome and physiology of their bacterial host?. Mol Microbiol 2019; 111:303–316 [View Article]
    [Google Scholar]
  17. Gilcrease EB, Casjens SR. The genome sequence of Escherichia coli tailed phage D6 and the diversity of Enterobacteriales circular plasmid prophages. Virology 2018; 515:203–214 [View Article]
    [Google Scholar]
  18. Adler BA, Kazakov AE, Zhong C, Liu H, Kutter E et al. The genetic basis of phage susceptibility, cross-resistance and host-range in Salmonella. Microbiology 2021; 167:001126 [View Article]
    [Google Scholar]
  19. Patchanee P, Chokesajjawatee N, Santiyanont P, Chuammitri P, Deeudom M et al. Characterisation of Salmonella enterica clones carrying mcr-1 plasmids in meat products and patients in Northern Thailand using long read sequencing. Int J Food Microbiol 2021; 358:109314 [View Article] [PubMed]
    [Google Scholar]
  20. Locke RK, Greig DR, Jenkins C, Dallman TJ, Cowley LA. Acquisition and loss of CTX-M plasmids in Shigella species associated with MSM transmission in the UK. Microb Genom 2021; 7:000644 [View Article]
    [Google Scholar]
  21. Sia CM, Greig DR, Day M, Hartman H, Painset A et al. The characterization of mobile colistin resistance (mcr) genes among 33 000 Salmonella enterica genomes from routine public health surveillance in England. Microb Genom 2020; 6:000331 [View Article]
    [Google Scholar]
  22. Greig DR, Dallman TJ, Hopkins KL, Jenkins C. MinION nanopore sequencing identifies the position and structure of bacterial antibiotic resistance determinants in a multidrug-resistant strain of enteroaggregative Escherichia coli. Microb Genom 2018; 4:000213 [View Article]
    [Google Scholar]
  23. Lee WWY, Mattock J, Greig DR, Langridge GC, Baker D et al. Characterization of a pESI-like plasmid and analysis of multidrug-resistant Salmonella enterica Infantis isolates in England and Wales. Microb Genom 2021; 7:000658 [View Article]
    [Google Scholar]
  24. Godbole G, McCann N, Jones SM, Dallman TJ, Brown M. Ceftriaxone-resistant Salmonella Typhi in a traveller returning from a mass gathering in Iraq. Lancet Infect Dis 2019; 19:467 [View Article] [PubMed]
    [Google Scholar]
  25. Chattaway MA, Gentle A, Nair S, Tingley L, Day M et al. Phylogenomics and antimicrobial resistance of Salmonella Typhi and Paratyphi A, B and C in England, 2016–2019. Microb Genom 2021; 7:000633 [View Article]
    [Google Scholar]
  26. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article] [PubMed]
    [Google Scholar]
  27. Tewolde R, Dallman T, Schaefer U, Sheppard CL, Ashton P et al. MOST: a modified MLST typing tool based on short read sequencing. PeerJ 2016; 4:e2308 [View Article] [PubMed]
    [Google Scholar]
  28. Achtman M, Wain J, Weill F-X, Nair S, Zhou Z et al. Multilocus sequence typing as a replacement for serotyping in Salmonella enterica. PLoS Pathog 2012; 8:e1002776 [View Article] [PubMed]
    [Google Scholar]
  29. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods 2012; 9:357–359 [View Article] [PubMed]
    [Google Scholar]
  30. 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]
  31. Day MR, Doumith M, Do Nascimento V, Nair S, Ashton PM et al. Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of Salmonella enterica serovars Typhi and Paratyphi. J Antimicrob Chemother 2018; 73:365–372 [View Article]
    [Google Scholar]
  32. Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother 2020; 75:3491–3500 [View Article]
    [Google Scholar]
  33. Day M, Doumith M, Jenkins C, Dallman TJ, Hopkins KL et al. Antimicrobial resistance in Shiga toxin-producing Escherichia coli serogroups O157 and O26 isolated from human cases of diarrhoeal disease in England, 2015. J Antimicrob Chemother 2017; 72:145–152 [View Article]
    [Google Scholar]
  34. Sadouki Z, Day MR, Doumith M, Chattaway MA, Dallman TJ et al. Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of Shigella sonnei isolated from cases of diarrhoeal disease in England and Wales, 2015. J Antimicrob Chemother 2017; 72:2496–2502 [View Article]
    [Google Scholar]
  35. Greig DR, Jenkins C, Gharbia SE, Dallman TJ. Analysis of a small outbreak of Shiga toxin-producing Escherichia coli O157:H7 using long-read sequencing. Microb Genom 2021; 7:000545 [View Article]
    [Google Scholar]
  36. Kolmogorov M, Yuan J, Lin Y, Pevzner PA. Assembly of long, error-prone reads using repeat graphs. Nat Biotechnol 2019; 37:540–546 [View Article] [PubMed]
    [Google Scholar]
  37. Yara DA, Greig DR, Gally DL, Dallman TJ, Jenkins C. Comparison of Shiga toxin-encoding bacteriophages in highly pathogenic strains of Shiga toxin-producing Escherichia coli O157:H7 in the UK. Microb Genom 2020; 6:000334 [View Article]
    [Google Scholar]
  38. Walker BJ, Abeel T, Shea T, Priest M, Abouelliel A et al. Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS One 2014; 9:e112963 [View Article] [PubMed]
    [Google Scholar]
  39. Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 2010; 26:589–595 [View Article] [PubMed]
    [Google Scholar]
  40. Vaser R, Sović I, Nagarajan N, Šikić M. Fast and accurate de novo genome assembly from long uncorrected reads. Genome Res 2017; 27:737–746 [View Article] [PubMed]
    [Google Scholar]
  41. 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 [View Article] [PubMed]
    [Google Scholar]
  42. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  43. Carattoli A, Hasman H. PlasmidFinder and in silico pMLST: identification and typing of plasmid replicons in whole-genome sequencing (WGS). Methods Mol Biol 2020; 2075:285–294 [View Article]
    [Google Scholar]
  44. Alikhan N-F, Petty NK, Ben Zakour NL, Beatson SA. BLAST Ring Image Generator (BRIG): simple prokaryote genome comparisons. BMC Genomics 2011; 12:402 [View Article] [PubMed]
    [Google Scholar]
  45. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990; 215:403–410 [View Article] [PubMed]
    [Google Scholar]
  46. Li H. Minimap2: pairwise alignment for nucleotide sequences. Bioinformatics 2018; 34:3094–3100 [View Article] [PubMed]
    [Google Scholar]
  47. Robinson JT, Thorvaldsdóttir H, Winckler W, Guttman M, Lander ES et al. Integrative genomics viewer. Nat Biotechnol 2011; 29:24–26 [View Article] [PubMed]
    [Google Scholar]
  48. Argimón S, Nagaraj G, Shamanna V, Sravani D, Vasanth AK et al. Circulation of third-generation cephalosporin resistant Salmonella Typhi in Mumbai, India. Clin Infect Dis 2022; 74:2234–2237 [View Article] [PubMed]
    [Google Scholar]
  49. Shin J, Ko KS. A plasmid bearing the bla(CTX-M-15) gene and phage P1-like sequences from a sequence type 11 Klebsiella pneumoniae isolate. Antimicrob Agents Chemother 2015; 59:6608–6610 [View Article]
    [Google Scholar]
  50. François Watkins LK, Winstead A, Appiah GD, Friedman CR, Medalla F et al. Update on extensively drug-resistant Salmonella serotype Typhi infections among travelers to or from Pakistan and report of ceftriaxone-resistant Salmonella serotype Typhi infections among travelersI to Iraq – United States, 2018–2019. MMWR Morb Mortal Wkly Rep 2020; 69:618–622 [View Article]
    [Google Scholar]
  51. Hensel M. Evolution of pathogenicity islands of Salmonella enterica. Int J Med Microbiol 2004; 294:95–102 [View Article] [PubMed]
    [Google Scholar]
  52. Suez J, Porwollik S, Dagan A, Marzel A, Schorr YI et al. Virulence gene profiling and pathogenicity characterization of non-typhoidal Salmonella accounted for invasive disease in humans. PLoS One 2013; 8:e58449 [View Article] [PubMed]
    [Google Scholar]
  53. Hrabák J, Empel J, Bergerová T, Fajfrlík K, Urbásková P et al. International clones of Klebsiella pneumoniae and Escherichia coli with extended-spectrum β-lactamases in a Czech hospital. J Clin Microbiol 2009; 47:3353–3357 [View Article]
    [Google Scholar]
  54. Fitzgerald SF, Lupolova N, Shaaban S, Dallman TJ, Greig D et al. Genome structural variation in Escherichia coli O157:H7. Microb Genom 2021; 7:000682 [View Article]
    [Google Scholar]
  55. Clokie MRJ, Kropinski AM. Bacteriophages: Methods and Protocols New York: Humana Press; 2009
    [Google Scholar]
  56. Sirén K, Millard A, Petersen B, Gilbert MTP, Clokie MRJ et al. Rapid discovery of novel prophages using biological feature engineering and machine learning. NAR Genom Bioinform 2021; 3:lqaa109 [View Article] [PubMed]
    [Google Scholar]
  57. Durrant MG, Li MM, Siranosian BA, Montgomery SB, Bhatt AS. A bioinformatic analysis of integrative mobile genetic elements highlights their role in bacterial adaptation. Cell Host Microbe 2020; 27:140–153 [View Article] [PubMed]
    [Google Scholar]
  58. Song W, Sun H-X, Zhang C, Cheng L, Peng Y et al. Prophage Hunter: an integrative hunting tool for active prophages. Nucleic Acids Res 2019; 47:W74–W80 [View Article] [PubMed]
    [Google Scholar]
  59. Kieft K, Zhou Z, Anantharaman K. VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences. Microbiome 2020; 8:90 [View Article] [PubMed]
    [Google Scholar]
  60. Akhter S, Aziz RK, Edwards RA. PhiSpy: a novel algorithm for finding prophages in bacterial genomes that combines similarity- and composition-based strategies. Nucleic Acids Res 2012; 40:e126 [View Article] [PubMed]
    [Google Scholar]
  61. Amgarten D, Braga LPP, da Silva AM, Setubal JC. MARVEL, a tool for prediction of bacteriophage sequences in metagenomic bins. Front Genet 2018; 9:304 [View Article] [PubMed]
    [Google Scholar]
  62. Arndt D, Marcu A, Liang Y, Wishart DS. PHAST, PHASTER and PHASTEST: tools for finding prophage in bacterial genomes. Brief Bioinform 2019; 20:1560–1567 [View Article] [PubMed]
    [Google Scholar]
  63. Starikova EV, Tikhonova PO, Prianichnikov NA, Rands CM, Zdobnov EM et al. Phigaro: high-throughput prophage sequence annotation. Bioinformatics 2020; 36:3882–3884 [View Article] [PubMed]
    [Google Scholar]
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