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Volume 7, Issue 8

Acquisition and loss of CTX-M plasmids in species associated with MSM transmission in the UK Open Access

Abstract

Shigellosis in men who have sex with men (MSM) is caused by multidrug resistant Shigellae, exhibiting resistance to antimicrobials including azithromycin, ciprofloxacin and more recently the third-generation cephalosporins. We sequenced four -positive MSM isolates (2018–20) using Oxford Nanopore Technologies; three (identified as two MSM clade 2, one MSM clade 5) and one 3a, to explore AMR context. All isolates harboured Tn7/Int2 chromosomal integrons, whereas 3a contained the Resistance Locus. All strains harboured IncFII pKSR100-like plasmids (67-83kbp); where present was located on these plasmids flanked by IS and IS, however was lost in 3a during storage between Illumina and Nanopore sequencing. IncFII AMR regions were mosaic and likely reorganised by IS; three of the four plasmids contained azithromycin-resistance genes ) and ) and one harboured the pKSR100 integron. Additionally, all isolates possessed a large IncB/O/K/Z plasmid, two of which carried and ). Monitoring the transmission of mobile genetic elements with co-located AMR determinants is necessary to inform empirical treatment guidance and clinical management of MSM-associated shigellosis.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antimicrobial resistance , CTX-M , ESBL , MSM , public health and Shigella
© 2021 The Authors
  • 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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2021-08-24
2024-04-25
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References

  1. Chiou CS, Izumiya H, Kawamura M, Liao YS, Su YS et al. The worldwide spread of ciprofloxacin-resistant Shigella sonnei among HIV-infected men who have sex with men, Taiwan. Clin Microbiol Infect 2016; 22:383 [View Article]
     [Google Scholar]
  2. DuPont HL, Levine MM, Hornick RB, Formal SB. Inoculum size in shigellosis and implications for expected mode of transmission. J Infect Dis 1989; 159:1126–1128 [View Article]
     [Google Scholar]
  3. 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 [View Article] [PubMed]
     [Google Scholar]
  4. Schroeder GN, Hilbi H. Molecular pathogenesis of shigella spp.: Controlling host cell signaling, invasion, and death by type iii secretion. Clin Microbiol Rev 2008; 21:134–156 [View Article] [PubMed]
     [Google Scholar]
  5. 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 [View Article] [PubMed]
     [Google Scholar]
  6. Bardhan P, Faruque ASG, Naheed A, Sack DA. Decrease in shigellosis-related deaths without shigella spp.- specific interventions, Asia. Emerg Infect Dis 2010; 16:1718–1723 [View Article] [PubMed]
     [Google Scholar]
  7. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): A prospective, case-control study. The Lancet 2013; 382:209–222 [View Article]
     [Google Scholar]
  8. Baker KS, Dallman TJ, Field N, Childs T, Mitchell H et al. Genomic epidemiology of Shigella in the United Kingdom shows transmission of pathogen sublineages and determinants of antimicrobial resistance. Scientific Reports 2018; 8:
     [Google Scholar]
  9. 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 fexneri and s. Sonnei in England, 2004 to end of February 2015. Eurosurveillance 2015; 20:1–5
     [Google Scholar]
  10. Williams PCM, Berkley JA. Guidelines for the treatment of dysentery (shigellosis): a systematic review of the evidence. Paediatrics and International Child Health 2018; 38:
     [Google Scholar]
  11. Holt KE, Baker S, Weill FX, Holmes EC, Kitchen A et al. Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe. Nat Genet 2012; 44:1056–1059 [View Article] [PubMed]
     [Google Scholar]
  12. Rajakumar K, Bulach D, Davies J, Ambrose L, Sasakawa C et al. Identification of a chromosomal Shigella flexneri multi-antibiotic resistance locus which shares sequence and organizational similarity with the resistance region of the plasmid NR1. Plasmid 1997; 37:159–168 [View Article] [PubMed]
     [Google Scholar]
  13. Ye C, Lan R, Xia S, Zhang J, Sun Q et al. Emergence of a new multidrug-resistant serotype X variant in an epidemic clone of Shigella flexneri. J Clin Microbiol 2010; 48:419–426 [View Article] [PubMed]
     [Google Scholar]
  14. Chung The H, Boinett C, Pham Thanh D, Jenkins C, Weill F-X et al. Dissecting the molecular evolution of fluoroquinolone-resistant Shigella sonnei. Nat Commun 2019; 10:4828 [View Article] [PubMed]
     [Google Scholar]
  15. Baker KS, Dallman TJ, Field N, Childs T, Mitchell H et al. Horizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species. Nature Communications 2018; 9:1–10
     [Google Scholar]
  16. Mook P, McCormick J, Bains M, Cowley LA, Chattaway MA et al. ESBL-Producing and macrolide-resistant Shigella sonnei infections among men who have sex with men, England, 2015. Emerg Infect Dis 2016; 22:1948–1952 [View Article] [PubMed]
     [Google Scholar]
  17. Ingle DJ, Andersson P, Valcanis M, Barnden J, Gonçalves da Silva A et al. Prolonged outbreak of multidrug-resistant Shigella sonnei harbouring bla CTX-M-27 in Victoria, Australia. Antimicrob Agents Chemother 2020; 64: [View Article] [PubMed]
     [Google Scholar]
  18. Muthuirulandi Sethuvel DP, Veeraraghavan B, Vasudevan K, Devanga Ragupathi NK, Murugan D et al. Complete genome analysis of clinical Shigella strains reveals plasmid pSS1653 with resistance determinants: A triumph of hybrid approach. Gut Pathog 2019; 11:55 [View Article] [PubMed]
     [Google Scholar]
  19. Campos-Madueno EI, Bernasconi OJ, Moser AI, Keller PM, Luzzaro F et al. Rapid Increase of CTX-M-Producing Shigella sonnei Isolates in Switzerland: spread of common plasmids and International Clones. Antimicrobial Agents and Chemotherapy 202001057–20
     [Google Scholar]
  20. Arredondo-Alonso S, Willems RJ, van Schaik W, Schürch AC. On the (im)possibility of reconstructing plasmids from whole-genome short-read sequencing data. Microbial Genomics 2017; 3:10 [View Article]
     [Google Scholar]
  21. George S, Pankhurst L, Hubbard A, Votintseva A, Stoesser N et al. Resolving plasmid structures in enterobacteriaceae using the Minion nanopore sequencer: Assessment of Minion and Minion/illumina hybrid data assembly approaches. Microb Genom 2017; 3:e000118 [View Article]
     [Google Scholar]
  22. Sedlazeck FJ, Lee H, Darby CA, Schatz MC. Piercing the dark matter: Bioinformatics of long-range sequencing and mapping. Nat Rev Genet 2018; 19:329–346 [View Article] [PubMed]
     [Google Scholar]
  23. Bolger AM, Lohse M, Usadel B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article] [PubMed]
     [Google Scholar]
  24. De Coster W, D’Hert S, Schultz DT, Cruts M, Van Broeckhoven C. NanoPack: visualizing and processing long-read sequencing data. Bioinformatics 2018; 34:2666–2669 [View Article] [PubMed]
     [Google Scholar]
  25. 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]
  26. Wick RR, Judd LM, Gorrie CL, Holt KE. Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 2017; 13:e1005595 [View Article] [PubMed]
     [Google Scholar]
  27. Li H, Durbin R. Fast and accurate short read alignment with Burrows–Wheeler transform. Bioinformatics 2009; 25:1754–1760 [View Article] [PubMed]
     [Google Scholar]
  28. 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]
  29. 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]
  30. 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]
  31. Gurevich A, Saveliev V, Vyahhi N, Tesler G. QUAST: Quality assessment tool for genome assemblies. Bioinformatics 2013; 29:1072–1075 [View Article] [PubMed]
     [Google Scholar]
  32. 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]
  33. Darling AE, Mau B, Perna NT. Progressivemauve: Multiple genome alignment with gene gain, loss and rearrangement. PLoS ONE 2010; 5:e11147 [View Article] [PubMed]
     [Google Scholar]
  34. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
     [Google Scholar]
  35. Arredondo-Alonso S, Rogers MRC, Braat JC, Verschuuren TD, Top J et al. mlplasmids: a user-friendly tool to predict plasmid- and chromosome-derived sequences for single species. Microb Genom 2018; 4:e000224 [View Article] [PubMed]
     [Google Scholar]
  36. Larsen M, Cosentino S, Rasmussen S, Friis C, Hasman H et al. Multilocus sequence typing of total-genome-sequenced bacteria. J Clin Microbiol 2012; 50:1355–1361 [View Article] [PubMed]
     [Google Scholar]
  37. Varani AM, Siguier P, Gourbeyre E, Charneau V, Chandler M. ISsaga is an ensemble of web-based methods for high throughput identification and semi-automatic annotation of insertion sequences in prokaryotic genomes. Genome Biol 2011; 12:R30 [View Article] [PubMed]
     [Google Scholar]
  38. Carattoli A, Hasman H. PlasmidFinder and In silico pMLST: Identification and typing of plasmid replicons in whole-genome sequencing (WGS). In Methods in Molecular Biology Humana Press Inc; 2020 pp 285–294
     [Google Scholar]
  39. 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 [View Article] [PubMed]
     [Google Scholar]
  40. Alcock BP, Raphenya AR, Lau TTY, Tsang KK, Bouchard M et al. CARD 2020: antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Research 2019; 48:D517–D525
     [Google Scholar]
  41. Li H. Minimap2: Pairwise alignment for nucleotide sequences. Bioinformatics 2018; 34:3094–3100 [View Article] [PubMed]
     [Google Scholar]
  42. Milne I, Bayer M, Cardle L, Shaw P, Stephen G et al. Tablet-next generation sequence assembly visualization. Bioinformatics 2009; 26:401–402 [View Article] [PubMed]
     [Google Scholar]
  43. Xie Z, Tang H. ISEScan: Automated Identification of Insertion Sequence Elements in Prokaryotic Genomes Bioinformatics (Oxford, England: 2017 pp 3340–3347
     [Google Scholar]
  44. Dallman T, Ashton P, Schafer U, Jironkin A, Painset A et al. SnapperDB: a database solution for routine sequencing analysis of bacterial isolates. Bioinformatics 2018; 34:3028–3029 [View Article] [PubMed]
     [Google Scholar]
  45. Bardsley M, Jenkins C, Mitchell HD, Mikhail AFW, Baker KS et al. Persistent transmission of shigellosis in England is associated with a recently emerged multidrug-resistant strain of Shigella Sonnei. J Clin Microbiol 2020; 58:3 [View Article]
     [Google Scholar]
  46. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era. Mol Biol Evol 2020; 37:1530–1534 [View Article] [PubMed]
     [Google Scholar]
  47. Hawkey J, Paranagama K, Baker KS, Bengtsson RJ, Weill FX et al. Global population structure and genotyping framework for genomic surveillance of the major dysentery pathogen, Shigella sonnei. Nature Communications 2021; 12:1–12 [View Article]
     [Google Scholar]
  48. Hunt M, Bradley P, Lapierre SG, Heys S, Thomsit M et al. Antibiotic resistance prediction for Mycobacterium tuberculosis from genome sequence data with Mykrobe. Wellcome Open Res 2019; 4:191 [View Article] [PubMed]
     [Google Scholar]
  49. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods 2012; 9:357–359 [View Article] [PubMed]
     [Google Scholar]
  50. Sullivan MJ, Petty NK, Beatson SA. Easyfig: A genome comparison visualizer. Bioinformatics 2011; 27:1009–1010 [View Article] [PubMed]
     [Google Scholar]
  51. Petkau A, Stuart-Edwards M, Stothard P, van Domselaar G. Interactive microbial genome visualization with GView. Bioinformatics 2010; 26:3125–3126 [View Article] [PubMed]
     [Google Scholar]
  52. Alikhan NF, Petty NK, Ben Zakour NL, Beatson SA. blast Ring Image Generator (BRIG): Simple prokaryote genome comparisons. BMC Genomics 2011; 12:402 [PubMed]
     [Google Scholar]
  53. Yu G. Using ggtree to Visualize Data on Tree-Like Structures. Current Protocols in Bioinformatics 2020 [View Article]
     [Google Scholar]
  54. Buchrieser C, Glaser P, Rusniok C, Nedjari H, D’Hauteville H et al. The virulence plasmid pWR100 and the repertoire of proteins secreted by the type III secretion apparatus of Shigella flexneri. Mol Microbiol 2000; 38:760–771 [View Article] [PubMed]
     [Google Scholar]
  55. Faherty C, Harper JM, Shea-Donohue T, Barry EM, Kaper JB et al. Chromosomal and plasmid-encoded factors of Shigella flexneri induce secretogenic activity ex vivo. PLoS ONE 2012; 7:49980 [View Article]
     [Google Scholar]
  56. Mattock E, Blocker AJ. How do the virulence factors of shigella work together to cause disease. Front Cell Infect Microbiol 2017; 7:64 [View Article] [PubMed]
     [Google Scholar]
  57. 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 [View Article] [PubMed]
     [Google Scholar]
  58. Ranjbar R, Farahani A. Shigella: Antibiotic-resistance mechanisms and new horizons for treatment. Infect Drug Resist 2019; 12:3137–3167 [View Article] [PubMed]
     [Google Scholar]
  59. Ingle DJ, Easton M, Valcanis M, Seemann T, Kwong JC et al. Co-circulation of multidrug-resistant Shigella among men who have sex with men in Australia. Clin Infect Dis 2019; 69:1535–1544 [View Article] [PubMed]
     [Google Scholar]
  60. Yousfi K, Gaudreau C, Pilon PA, Lefebvre B, Walker M et al. Genetic mechanisms behind the spread of reduced susceptibility to azithromycin in Shigella strains isolated from men who have sex with men in Québec, Canada. Antimicrob Agents Chemother 2019; 63: [View Article] [PubMed]
     [Google Scholar]
  61. Trieu-Cuot P, Labigne-Roussel A, Courvalin P. An IS15 insertion generates an eight-base-pair duplication of the target DNA. Gene 1983; 24:125–129 [View Article] [PubMed]
     [Google Scholar]
  62. Klontz KC, Singh N. Treatment of drug-resistant Shigella infections. Expert Rev Anti Infect Ther 2015; 13:69–80 [View Article] [PubMed]
     [Google Scholar]
  63. Zamanlou S, Ahangarzadeh Rezaee M, Aghazadeh M, Ghotaslou R, Babaie F et al. Characterization of integrons, extended-spectrum β-lactamases, AmpC cephalosporinase, quinolone resistance, and molecular typing of Shigella spp. Infect Dis (Lond) 2018; 50:616–624 [View Article] [PubMed]
     [Google Scholar]
  64. Medeiros PHQS, Lima AÂM, Guedes MM, Havt A, Bona MD et al. Molecular characterization of virulence and antimicrobial resistance profile of Shigella species isolated from children with moderate to severe diarrhea in northeastern Brazil. Diagn Microbiol Infect Dis 2018; 90:198–205 [View Article] [PubMed]
     [Google Scholar]
  65. Sethuvel DPM, Anandan S, Michael JS, Murugan D, Neeravi A et al. Virulence gene profiles of Shigella species isolated from stool specimens in India: its association with clinical manifestation and antimicrobial resistance. Pathog Glob Health 2019; 113:173–179 [View Article] [PubMed]
     [Google Scholar]
  66. Cheasty T, Day M, Threlfall EJ. Increasing incidence of resistance to nalidixic acid in shigellas from humans in England and Wales: Implications for therapy. Clin Microbiol Infect 2004; 10:1033–1035 [View Article] [PubMed]
     [Google Scholar]
  67. The HC, Thanh DP, Holt KE, Thomson NR, Baker S. The genomic signatures of Shigella evolution, adaptation and geographical spread. Nat Rev Microbiol 2016; 14:235–250 [View Article] [PubMed]
     [Google Scholar]
  68. Bevan E, Jones A, Hawkey P. Global epidemiology of CTX-M β-lactamases: temporal and geographical shifts in genotype. J Antimicrob Chemother 2017; 72:2145–2155 [View Article] [PubMed]
     [Google Scholar]
  69. 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] [PubMed]
     [Google Scholar]
  70. 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 [View Article] [PubMed]
     [Google Scholar]
  71. Ruscher C, Werber D, Thoulass J, Zimmermann R, Eckardt M et al. Dating apps and websites as tools to reach anonymous sexual contacts during an outbreak of hepatitis A among men who have sex with men, Berlin, 2017. Eurosurveillance 2019; 24:1800460 [View Article]
     [Google Scholar]
  72. Liu G, Qian H, Tang B, Chen Y, Kang H et al. Prevalence and characterisation of third-generation cephalosporin-resistant Shigella flexneri isolates from Jiangsu Province, China, 2013–2015. J Glob Antimicrob Resist 2018; 15:283–287 [View Article] [PubMed]
     [Google Scholar]
  73. Hawkey J, Monk JM, Billman-Jacobe H, Palsson B, Holt KE. Impact of insertion sequences on convergent evolution of Shigella species. PLoS Genet 2020; 16:e1008931 [View Article] [PubMed]
     [Google Scholar]
  74. Partridge SR. Analysis of antibiotic resistance regions in Gram-negative bacteria. FEMS Microbiol Rev 2011; 35:820–855 [View Article] [PubMed]
     [Google Scholar]
  75. Harmer CJ, Moran RA, Hall RM. Movement of IS26-Associated antibiotic resistance genes occurs via a translocatable unit that includes a single IS26 and preferentially inserts adjacent to another IS26. mBio 2014; 5:e01801–14 [View Article] [PubMed]
     [Google Scholar]
  76. Mostafa HH, Cameron A, Taffner SM, Wang J, Malek A et al. Genomic surveillance of ceftriaxone-resistant Escherichia coli in Western New York suggests the extended-spectrum β-lactamase blaCTX-M-27 is emerging on distinct plasmids in ST38. Front Microbiol 2020; 11:1747 [View Article] [PubMed]
     [Google Scholar]
  77. He S, Hickman AB, Varani AM, Siguier P, Chandler M et al. Insertion sequence IS26 reorganizes plasmids in clinically isolated multidrug-resistant bacteria by replicative transposition. mBio 2015; 6:
     [Google Scholar]
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Acquisition and loss of CTX-M plasmids in Shigella species associated with MSM transmission in the UK
M Gen 7, 000644 (2021); https://doi.org/10.1099/mgen.0.000644
/content/journal/mgen/10.1099/mgen.0.000644
/content/journal/mgen/10.1099/mgen.0.000644
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