1887

Abstract

Fatal exudative dermatitis (FED) is a significant cause of death of red squirrels () on the island of Jersey in the Channel Islands where it is associated with a virulent clone of ST49. ST49 has been found in other hosts such as small mammals, pigs and humans, but the dynamics of carriage and disease of this clone, or any other lineage in red squirrels, is currently unknown. We used whole-genome sequencing to characterize 228 isolates from healthy red squirrels on Jersey, the Isle of Arran (Scotland) and Brownsea Island (England), from red squirrels showing signs of FED on Jersey and the Isle of Wight (England) and a small number of isolates from other hosts. was frequently carried by red squirrels on the Isle of Arran with strains typically associated with small ruminants predominating. For the Brownsea carriage, was less frequent and involved strains associated with birds, small ruminants and humans, while for the Jersey carriage was rare but ST49 predominated in diseased squirrels. By combining our data with publicly available sequences, we show that the carriage in red squirrels largely reflects frequent but facile acquisitions of strains carried by other hosts sharing their habitat (‘spillover’), possibly including, in the case of ST188, humans. Genome-wide association analysis of the ruminant lineage ST133 revealed variants in a small number of mostly bacterial-cell-membrane-associated genes that were statistically associated with squirrel isolates from the Isle of Arran, raising the possibility of specific adaptation to red squirrels in this lineage. In contrast there is little evidence that ST49 is a common carriage isolate of red squirrels and infection from reservoir hosts such as bank voles or rats, is likely to be driving the emergence of FED in red squirrels.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 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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2021-05-20
2022-01-24
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References

  1. Ballingall KT, McIntyre A, Lin Z, Timmerman N, Matthysen E et al. Limited diversity associated with duplicated class II MHC-DRB genes in the red squirrel population in the United Kingdom compared with continental Europe. Conservation Genetics 2016; 17:1171–1182 [View Article]
    [Google Scholar]
  2. Carroll B, Russell P, Gurnell J, Nettleton P, Sainsbury AW. Epidemics of squirrelpox virus disease in red squirrels (Sciurus vulgaris): temporal and serological findings. Epidemiol Infect 2009; 137:257–265 [View Article]
    [Google Scholar]
  3. Avanzi C, del-Pozo J, Benjak A, Stevenson K, Simpson VR et al. Red squirrels in the British Isles are infected with leprosy bacilli . Science 2016; 354:744–747 [View Article]
    [Google Scholar]
  4. Blackett TA, Simpson VR, Haugland S, Everest DJ, Muir CF et al. Mortalities, amyloidosis and other diseases in free-living red squirrels (Sciurus vulgaris) on Jersey, Channel Islands. Vet Rec 2018; 183:503 [View Article][PubMed]
    [Google Scholar]
  5. Simpson VR, Hargreaves J, Everest DJ, Baker AS, Booth PA et al. Mortality in red squirrels (Sciurus vulgaris) associated with exudative dermatitis. Vet Rec 2010; 167:59–62 [View Article]
    [Google Scholar]
  6. Simpson VR, Davison NJ, Kearns AM, Pichon B, Hudson LO et al. Association of a lukM-positive clone of Staphylococcus aureus with fatal exudative dermatitis in red squirrels (Sciurus vulgaris). Vet Microbiol 2013; 162:987–991 [View Article]
    [Google Scholar]
  7. Mrochen DM, Schulz D, Fischer S, Jeske K, El Gohary H et al. Wild rodents and shrews are natural hosts of Staphylococcus aureus . Int J Med Microbiol 2018; 308:590–597 [View Article]
    [Google Scholar]
  8. Raafat D, Mrochen DM, Al’Sholui F, Heuser E, Ryll R et al. Molecular epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in wild, captive and laboratory rats: effect of habitat on the nasal S. aureus population. Toxins 2020; 12:80 [View Article]
    [Google Scholar]
  9. Overesch G, Büttner S, Rossano A, Perreten V. The increase of methicillin-resistant Staphylococcus aureus (MRSA) and the presence of an unusual sequence type ST49 in slaughter pigs in Switzerland. BMC Vet Res 2011; 7:30 [View Article]
    [Google Scholar]
  10. Davis R, Hossain MJ, Liles MR, Panizzi P. Complete genome sequence of Staphylococcus aureus Tager 104, a sequence type 49 ancestor. Genome Announc 2013; 1: [View Article]
    [Google Scholar]
  11. Trübe P, Hertlein T, Mrochen DM, Schulz D, Jorde I et al. Bringing together what belongs together: optimizing murine infection models by using mouse-adapted Staphylococcus aureus strains. Int J Med Microbiol 2019; 309:26–38 [View Article]
    [Google Scholar]
  12. Hoekstra J, Rutten V, Sommeling L, van Werven T, Spaninks M et al. High Production of LukMF’ in Staphylococcus aureus Field Strains Is Associated with Clinical Bovine Mastitis. Toxins 10:200 [View Article]
    [Google Scholar]
  13. Schlotter K, Ehricht R, Hotzel H, Monecke S, Pfeffer M et al. Leukocidin genes lukF-P83 and lukM are associated with Staphylococcus aureus clonal complexes 151, 479 and 133 isolated from bovine udder infections in Thuringia, Germany. Vet Res 2012; 43:42 [View Article]
    [Google Scholar]
  14. Vrieling M, Koymans KJ, Heesterbeek DAC, Aerts PC, Rutten V et al. Bovine Staphylococcus aureus secretes the leukocidin LukMF′ to kill migrating neutrophils through CCR1. MBio 2015; 6:e00335 [View Article]
    [Google Scholar]
  15. Schilling A-K, van Hooij A, Corstjens P, Lurz PWW, DelPozo J et al. Detection of humoral immunity to mycobacteria causing leprosy in Eurasian red squirrels (Sciurus vulgaris) using a quantitative rapid test. Eur J Wildl Res 2019; 65: [View Article]
    [Google Scholar]
  16. Wight Squirrel Project Wight squirrel project. http://www.wightsquirrels.co.uk/ 11 November 2020
  17. PubMLST Public databases for molecular typing and microbial genome diversity. https://pubmlst.org/ accessed 24 Sep 2020
  18. National Library of Medicine (US) National Center for Biotechnology Information Genbank 1982 https://www.ncbi.nlm.nih.gov/nucleotide/ accessed 11 Nov 2020
  19. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article]
    [Google Scholar]
  20. Andrews S. Fastqc: A quality control tool for high throughput sequence data. http://www.bioinformatics.babraham.ac.uk/projects/fastqc/
  21. 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 [View Article]
    [Google Scholar]
  22. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article]
    [Google Scholar]
  23. 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]
    [Google Scholar]
  24. Wick RR, Schultz MB, Zobel J, Holt KE. Bandage: interactive visualization of de novo genome assemblies: Fig. 1. Bioinformatics 2015; 31:3350–3352 [View Article]
    [Google Scholar]
  25. Seeman T MLST. Github. https://github.com/tseemann/mlst
  26. Seeman T. snippy: fast bacterial variant calling from NGS reads. https://github.com/tseemann/snippy ; 2015
  27. Seeman T. snp-dists; Convert a FASTA alignment to SNP distance matrix. https://github.com/tseemann/snp-dists .
  28. 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]
    [Google Scholar]
  29. Kozlov AM, Darriba D, Flouri T, Morel B, Stamatakis A. RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 2019; 35:4453–4455 [View Article]
    [Google Scholar]
  30. Letunic I, Bork P. Interactive tree of life (iTOL) V4: recent updates and new developments. Nucleic Acids Res 2019; 47:W256–W259 [View Article]
    [Google Scholar]
  31. Carver T, Harris SR, Berriman M, Parkhill J, McQuillan JA. Artemis: an integrated platform for visualization and analysis of high-throughput sequence-based experimental data. Bioinformatics 2012; 28:464–469 [View Article]
    [Google Scholar]
  32. Sievers F, Higgins DG. Clustal omega for making accurate alignments of many protein sequences. Protein Science 2018; 27:135–145 [View Article]
    [Google Scholar]
  33. Waterhouse AM, Procter JB, Martin DMA, Clamp M, Barton GJ. Jalview Version 2--a multiple sequence alignment editor and analysis workbench. Bioinformatics 2009; 25:1189–1191 [View Article]
    [Google Scholar]
  34. Sullivan MJ, Petty NK, Beatson SA. Easyfig: a genome comparison visualizer. Bioinformatics 2011; 27:1009–1010 [View Article]
    [Google Scholar]
  35. 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]
    [Google Scholar]
  36. Seeman T. Abricate; Mass screening of contigs for antimicrobial resistance or virulence genes. https://github.com/tseemann/abricate .
  37. 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]
    [Google Scholar]
  38. Chen L, Zheng D, Liu B, Yang J, VFDB JQ. Hierarchical and refined dataset for big data analysis-10 years on. Nucleic Acids Res 2016; 2016:D694–697
    [Google Scholar]
  39. 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]
    [Google Scholar]
  40. Jia B, Raphenya AR, Alcock B, Waglechner N, Guo P et al. Card 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res 2017; 45:D566–D573 [View Article]
    [Google Scholar]
  41. Gupta SK, Padmanabhan BR, Diene SM, Lopez-Rojas R, Kempf M et al. ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes. Antimicrob Agents Chemother 2014; 58:212–220 [View Article]
    [Google Scholar]
  42. 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]
    [Google Scholar]
  43. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol 1990; 215:403–410 [View Article]
    [Google Scholar]
  44. Antipov D, Hartwick N, Shen M, Raiko M, Lapidus A et al. plasmidSPAdes: assembling plasmids from whole genome sequencing data. Bioinformatics 2016; 151:btw493 [View Article]
    [Google Scholar]
  45. Robertson J, Nash JHE. MOB-suite: software tools for clustering, reconstruction and typing of plasmids from draft assemblies. Microb Genom 2018; 4: [View Article]
    [Google Scholar]
  46. Lees JA, Galardini M, Bentley SD, Weiser JN, Corander J. pyseer: a comprehensive tool for microbial pangenome-wide association studies. Bioinformatics 2018; 34:4310–4312 [View Article]
    [Google Scholar]
  47. van Alen S, Ballhausen B, Kaspar U, Köck R, Becker K. Prevalence and genomic structure of bacteriophage phi3 in Human-Derived Livestock-associated Methicillin-Resistant Staphylococcus aureus Isolates from 2000 to 2015. J Clin Microbiol 2018; 56: [View Article]
    [Google Scholar]
  48. Merz A, Stephan R, Johler S. Staphylococcus aureus isolates from goat and sheep milk seem to be closely related and differ from isolates detected from bovine milk. Front Microbiol 2016; 7:319 [View Article]
    [Google Scholar]
  49. Guinane CM, Ben Zakour NL, Tormo-Mas MA, Weinert LA, Lowder BV et al. Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation. Genome Biol Evol 2010; 2:454–466 [View Article]
    [Google Scholar]
  50. Sheppard SK, Guttman DS, Fitzgerald JR. Population genomics of bacterial host adaptation. Nat Rev Genet 2018; 19:549–565 [View Article]
    [Google Scholar]
  51. Murray S, Pascoe B, Méric G, Mageiros L, Yahara K et al. Recombination-Mediated host adaptation by avian Staphylococcus aureus . Genome Biol Evol 2017; 9:830–842 [View Article]
    [Google Scholar]
  52. Simpson S, Blampied N, Peniche G, Dozières A, Blackett T et al. Genetic structure of introduced populations: 120-year-old DNA footprint of historic introduction in an insular small mammal population. Ecol Evol 2013; 3:614–628 [View Article]
    [Google Scholar]
  53. Hall MD, Holden MTG, Srisomang P, Mahavanakul W, Wuthiekanun V et al. Improved characterisation of MRSA transmission using within-host bacterial sequence diversity. eLife 2019; 8:e46402 [View Article]
    [Google Scholar]
  54. Senghore M, Bayliss SC, Kwambana-Adams BA, Foster-Nyarko E, Manneh J et al. Transmission of Staphylococcus aureus from humans to green monkeys in the Gambia as revealed by whole-genome sequencing. Appl Environ Microbiol 2016; 82:5910–5917 [View Article]
    [Google Scholar]
  55. Sakr A, Brégeon F, Mège J-L, Rolain J-M, Blin O. Staphylococcus aureus nasal colonization: an update on mechanisms, epidemiology, risk factors, and subsequent infections. Front Microbiol 2018; 9: [View Article]
    [Google Scholar]
  56. Monecke S, Gavier-Widén D, Hotzel H, Peters M, Guenther S et al. Diversity of Staphylococcus aureus isolates in European wildlife. PLoS One 2016; 11:e0168433 [View Article]
    [Google Scholar]
  57. Smith EM, Needs PF, Manley G, Green LE. Global distribution and diversity of ovine-associated Staphylococcus aureus . Infection, Genetics and Evolution 2014; 22:208–215 [View Article]
    [Google Scholar]
  58. Agabou A, Ouchenane Z, Ngba Essebe C, Khemissi S, Chehboub M et al. Emergence of nasal carriage of ST80 and ST152 PVL+ Staphylococcus aureus isolates from livestock in Algeria. Toxins 9:303 [View Article]
    [Google Scholar]
  59. Luzzago C, Lauzi S, Ehricht R, Monecke S, Trogu T et al. Staphylococcus aureus nasal and intestinal carriage by free-ranging red deer: evidence of human, domestic and wild animal lineages. Int J Infect Dis 2019; 79:21–22 [View Article]
    [Google Scholar]
  60. Lowder BV, Guinane CM, Ben Zakour NL, Weinert LA, Conway-Morris A et al. Recent human-to-poultry host jump, adaptation, and pandemic spread of Staphylococcus aureus . Proc Natl Acad Sci U S A 2009; 106:19545–19550 [View Article]
    [Google Scholar]
  61. Lim S-K, Nam H-M, Park H-J, Lee H-S, Choi M-J. Prevalence and characterization of methicillin-resistant Staphylococcus aureus in RAW meat in Korea. J Microbiol Biotechnol 2010; 20:775–778
    [Google Scholar]
  62. Wang Y, Liu Q, Liu Q, Gao Q, Lu H et al. Phylogenetic analysis and virulence determinant of the host-adapted Staphylococcus aureus lineage ST188 in China. Emerg Microbes Infect 2018; 7:1–11 [View Article]
    [Google Scholar]
  63. Rasmussen SL, Larsen J, van Wijk RE, Jones OR, Berg TB et al. European hedgehogs (Erinaceus europaeus) as a natural reservoir of methicillin-resistant Staphylococcus aureus carrying mecC in Denmark. PLoS One 2019; 14:e0222031 [View Article]
    [Google Scholar]
  64. García-Álvarez L, Holden MTG, Lindsay H, Webb CR, Brown DFJ et al. Meticillin-Resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study. Lancet Infect Dis 2011; 11:595–603 [View Article]
    [Google Scholar]
  65. Lee DC, Kananurak A, Tran MT, Connolly PA, Polage CR et al. Bacterial colonization of the hospitalized newborn: competition between Staphylococcus aureus and Staphylococcus epidermidis . Pediatr Infect Dis J 2019; 38:682–686 [View Article]
    [Google Scholar]
  66. Hau SJ, Sun J, Davies PR, Frana TS, Nicholson TL. Comparative prevalence of immune evasion complex genes associated with β-hemolysin converting bacteriophages in MRSA ST5 isolates from swine, swine facilities, humans with swine contact, and humans with no swine contact. PLoS One 2015; 10:e0142832 [View Article]
    [Google Scholar]
  67. McCarthy AJ, Loeffler A, Witney AA, Gould KA, Lloyd DH et al. Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo. Genome Biol Evol 2014; 6:2697–2708 [View Article]
    [Google Scholar]
  68. Bacigalupe R, Tormo-Mas María Ángeles, Penadés JR, Fitzgerald JR. A multihost bacterial pathogen overcomes continuous population bottlenecks to adapt to new host species. Sci Adv 2019; 5:eaax0063 [View Article]
    [Google Scholar]
  69. Viana D, Comos M, McAdam PR, Ward MJ, Selva L et al. A single natural nucleotide mutation alters bacterial pathogen host tropism. Nat Genet 2015; 47:361–366 [View Article]
    [Google Scholar]
  70. Laabei M, Recker M, Rudkin JK, Aldeljawi M, Gulay Z et al. Predicting the virulence of MRSA from its genome sequence. Genome Res 2014; 24:839–849 [View Article]
    [Google Scholar]
  71. Harris S. A Review of British Mammals: Population Estimates and Conservation Status of British Mammals Other Than Cetaceans Peterborough: The Joint Nature Conservation Committee; 1995
    [Google Scholar]
  72. Hadfield J, Croucher NJ, Goater RJ, Abudahab K, Aanensen DM et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics 2018; 34:292–293 [View Article]
    [Google Scholar]
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