1887

Abstract

is a major etiological agent of clinical and subclinical bovine mastitis. The versatile and adaptative evolutionary strategies of this bacterium have challenged mastitis control and prevention globally, and the high incidence of mastitis increases concerns about antimicrobial resistance (AMR) and zoonosis. This study aims to describe the evolutionary relationship between bovine intramammary infection (IMI)-associated and human pathogenic and further elucidate the specific genetic composition that leads to the emergence of successful bovine IMI-associated lineages. We performed a phylogenomic analysis of 187 . isolates that originated from either dairy cattle or humans. Our results revealed that bovine IMI-associated isolates showed distinct clades compared to human-originated isolates. From a pan-genome analysis, 2070 core genes were identified. Host-specific genes and clonal complex (CC)-specific genes were also identified in bovine isolates, mostly located in mobile genetic elements (MGEs). Additionally, the genome sequences of three apparent human-adapted isolates (two from CC97 and one from CC8), isolated from bovine mastitis samples, may provide an snapshot of the genomic characteristics in early host spillover events. Virulence and AMR genes were not conserved among bovine IMI-associated isolates. Restriction-modification (R-M) genes in bovine IMI-associated demonstrated that the Type I R-M system was lineage-specific and Type II R-M system was sequence type (ST)-specific. The distribution of exclusive, virulence, and AMR genes were closely correlated with the presence of R-M systems in , suggesting that R-M systems may contribute to shaping clonal diversification by providing a genetic barrier to the horizontal gene transfer (HGT). Our findings indicate that the CC or ST lineage-specific R-M systems may limit genetic exchange between bovine-adapted isolates from different lineages.

Funding
This study was supported by the:
  • NSERC (Award 2015-05916)
    • Principle Award Recipient: FrançoisMalouin
  • NSERC CREATE in Milk Quality
    • Principle Award Recipient: ÉlodieDemontier
  • NSERC CREATE in Milk Quality
    • Principle Award Recipient: AlexisDube-Duquette
  • NSERC CREATE in Milk Quality
    • Principle Award Recipient: DongyunJung
  • NSERC CREATE in Milk Quality
    • Principle Award Recipient: SoyounPark
  • Op+lait Subvention Nouvelles Initiatives 2018/2019
    • Principle Award Recipient: JenniferRonholm
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2022-02-18
2022-05-18
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References

  1. Watts JL. Etiological agents of bovine mastitis. Vet Microbiol 1988; 16:41–66 [View Article] [PubMed]
    [Google Scholar]
  2. Fox LK, Zadoks RN, Gaskins CT. Biofilm production by Staphylococcus aureus associated with intramammary infection. Vet Microbiol 2005; 107:295–299 [View Article] [PubMed]
    [Google Scholar]
  3. Hébert A, Sayasith K, Sénéchal S, Dubreuil P, Lagacé J. Demonstration of intracellular Staphylococcus aureus in bovine mastitis alveolar cells and macrophages isolated from naturally infected cow milk. FEMS Microbiol Lett 2000; 193:57–62 [View Article] [PubMed]
    [Google Scholar]
  4. Atalla H, Gyles C, Mallard B. Persistence of a Staphylococcus aureus small colony variants (S. aureus SCV) within bovine mammary epithelial cells. Vet Microbiol 2010; 143:319–328 [View Article] [PubMed]
    [Google Scholar]
  5. Rainard P, Foucras G, Fitzgerald JR, Watts JL, Koop G et al. Knowledge gaps and research priorities in Staphylococcus aureus mastitis control. Transbound Emerg Dis 2018; 65 Suppl 1:149–165 [View Article] [PubMed]
    [Google Scholar]
  6. Sadykov MR. Restriction-modification systems as a barrier for genetic manipulation of Staphylococcus aureus. Methods Mol Biol 2016; 1373:9–23 [View Article]
    [Google Scholar]
  7. Park S, Ronholm J. Staphylococcus aureus in agriculture: lessons in evolution from a multispecies pathogen. Clin Microbiol Rev 2021; 34:e00182-20 [View Article]
    [Google Scholar]
  8. Matuszewska M, Murray GGR, Harrison EM, Holmes MA, Weinert LA. The evolutionary genomics of host specificity in Staphylococcus aureus. Trends Microbiol 2020; 28:465–477 [View Article]
    [Google Scholar]
  9. Herron-Olson L, Fitzgerald JR, Musser JM, Kapur V, Ahmed N. Molecular correlates of host specialization in Staphylococcus aureus. PLoS ONE 2007; 2:e1120 [View Article] [PubMed]
    [Google Scholar]
  10. Naushad S, Nobrega DB, Naqvi SA, Barkema HW, De Buck J et al. Genomic analysis of bovine Staphylococcus aureus isolates from milk to elucidate diversity and determine the distributions of antimicrobial and virulence genes and their association with mastitis. mSystems 2020; 5:e00063-20 [View Article] [PubMed]
    [Google Scholar]
  11. Vrieling M, Koymans KJ, Heesterbeek DAC, Aerts PC, Rutten VPMG et al. Bovine Staphylococcus aureus Secretes the Leukocidin LukMF’ To Kill Migrating Neutrophils through CCR1. mBio 2015; 6:e00335 [View Article] [PubMed]
    [Google Scholar]
  12. Viana D, Blanco J, Tormo-Más MA, Selva L, Guinane CM et al. Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI-carried variants of von Willebrand factor-binding protein. Mol Microbiol 2010; 77:1583–1594 [View Article] [PubMed]
    [Google Scholar]
  13. Cuny C, Wieler LH, Witte W. Livestock-Associated MRSA: the impact on humans. Antibiotics (Basel) 2015; 4:521–543 [View Article]
    [Google Scholar]
  14. Saini V, McClure JT, Scholl DT, DeVries TJ, Barkema HW. Herd-level association between antimicrobial use and antimicrobial resistance in bovine mastitis Staphylococcus aureus isolates on Canadian dairy farms. J Dairy Sci 2012; 95:1921–1929 [View Article] [PubMed]
    [Google Scholar]
  15. Haran KP, Godden SM, Boxrud D, Jawahir S, Bender JB et al. Prevalence and characterization of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus, isolated from bulk tank milk from Minnesota dairy farms. J Clin Microbiol 2012; 50:688–695 [View Article] [PubMed]
    [Google Scholar]
  16. Yang F, Wang Q, Wang X, Wang L, Xiao M et al. Prevalence of blaZ gene and other virulence genes in penicillin-resistant Staphylococcus aureus isolated from bovine mastitis cases in Gansu, China. Turk J Vet Anim Sci 2015; 39:634–636 [View Article]
    [Google Scholar]
  17. Bagcigil AF, Taponen S, Koort J, Bengtsson B, Myllyniemi A-L et al. Genetic basis of penicillin resistance of S. aureus isolated in bovine mastitis. Acta Vet Scand 2012; 54:69 [View Article] [PubMed]
    [Google Scholar]
  18. Jamali H, Radmehr B, Ismail S. Short communication: prevalence and antibiotic resistance of Staphylococcus aureus isolated from bovine clinical mastitis. J Dairy Sci 2014; 97:2226–2230 [View Article] [PubMed]
    [Google Scholar]
  19. Marques VF, Motta CC, Soares BS, de Melo DA, Coelho SMO et al. Biofilm production and beta-lactamic resistance in Brazilian Staphylococcus aureus isolates from bovine mastitis. Braz J Microbiol 2017; 48:118–124 [View Article] [PubMed]
    [Google Scholar]
  20. Klibi A, Jouini A, Gómez P, Slimene K, Ceballos S et al. Molecular characterization and clonal diversity of methicillin-resistant and -susceptible Staphylococcus aureus isolates of milk of cows with clinical mastitis in Tunisia. Microb Drug Resist 2018; 24:1210–1216 [View Article] [PubMed]
    [Google Scholar]
  21. Schmidt T, Kock MM, Ehlers MM. Molecular characterization of Staphylococcus aureus isolated from bovine mastitis and close human contacts in South African dairy herds: genetic diversity and inter-species host transmission. Front Microbiol 2017; 8:511 [View Article] [PubMed]
    [Google Scholar]
  22. Käppeli N, Morach M, Corti S, Eicher C, Stephan R et al. Staphylococcus aureus related to bovine mastitis in Switzerland: Clonal diversity, virulence gene profiles, and antimicrobial resistance of isolates collected throughout 2017. J Dairy Sci 2019; 102:3274–3281 [View Article] [PubMed]
    [Google Scholar]
  23. Waldron DE, Lindsay JA. Sau1: a novel lineage-specific type I restriction-modification system that blocks horizontal gene transfer into Staphylococcus aureus and between S. aureus isolates of different lineages. J Bacteriol 2006; 188:5578–5585 [View Article] [PubMed]
    [Google Scholar]
  24. Lindsay JA, Holden MTG. Staphylococcus aureus: superbug, super genome?. Trends Microbiol 2004; 12:378–385 [View Article] [PubMed]
    [Google Scholar]
  25. Roberts RJ, Belfort M, Bestor T, Bhagwat AS, Bickle TA et al. A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes. Nucleic Acids Res 2003; 31:1805–1812 [View Article] [PubMed]
    [Google Scholar]
  26. Roberts GA, Houston PJ, White JH, Chen K, Stephanou AS et al. Impact of target site distribution for Type I restriction enzymes on the evolution of methicillin-resistant Staphylococcus aureus (MRSA) populations. Nucleic Acids Res 2013; 41:7472–7484 [View Article] [PubMed]
    [Google Scholar]
  27. Corvaglia AR, François P, Hernandez D, Perron K, Linder P et al. A type III-like restriction endonuclease functions as a major barrier to horizontal gene transfer in clinical Staphylococcus aureus strains. Proc Natl Acad Sci U S A 2010; 107:11954–11958 [View Article] [PubMed]
    [Google Scholar]
  28. Lee JYH, Carter GP, Pidot SJ, Guérillot R, Seemann T et al. Mining the methylome reveals extensive diversity in Staphylococcus epidermidis restriction modification. mBio 2019; 10:e02451-19 [View Article] [PubMed]
    [Google Scholar]
  29. Bogdanova E, Djordjevic M, Papapanagiotou I, Heyduk T, Kneale G et al. Transcription regulation of the type II restriction-modification system AhdI. Nucleic Acids Res 2008; 36:1429–1442 [View Article] [PubMed]
    [Google Scholar]
  30. Roberts RJ, Vincze T, Posfai J, Macelis D. REBASE: restriction enzymes and methyltransferases. Nucleic Acids Res 2003; 31:418–420 [View Article] [PubMed]
    [Google Scholar]
  31. Park S, Jung D, Dufour S, Ronholm J, Dunning Hotopp JC. Draft genome sequences of 27 Staphylococcus aureus strains and 3 Staphylococcus species strains isolated from bovine intramammary infections. Microbiol Resour Announc 2020; 9:19 [View Article]
    [Google Scholar]
  32. Dufour S, Labrie J, Jacques M, Rasko D. The mastitis pathogens culture collection. Microbiol Resour Announc 2019; 8:15 [View Article]
    [Google Scholar]
  33. Demontier E, Dubé-Duquette A, Brouillette E, Larose A, Ster C et al. Relative virulence of Staphylococcus aureus bovine mastitis strains representing the main Canadian spa types and clonal complexes as determined using in vitro and in vivo mastitis models. J Dairy Sci 2021; 104:11904–11921 [View Article] [PubMed]
    [Google Scholar]
  34. Jung D, Park S, Ruffini J, Dussault F, Dufour S et al. Comparative genomic analysis of Escherichia coli isolates from cases of bovine clinical mastitis identifies nine specific pathotype marker genes. Microb Genom 2021; 7: [View Article] [PubMed]
    [Google Scholar]
  35. Okonechnikov K, Conesa A, García-Alcalde F. Qualimap 2: advanced multi-sample quality control for high-throughput sequencing data. Bioinformatics 2016; 32:292–294 [View Article] [PubMed]
    [Google Scholar]
  36. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  37. Tong SYC, Schaumburg F, Ellington MJ, Corander J, Pichon B et al. Novel staphylococcal species that form part of a Staphylococcus aureus-related complex: the non-pigmented Staphylococcus argenteus sp. nov. and the non-human primate-associated Staphylococcus schweitzeri sp. nov. Int J Syst Evol Microbiol 2015; 65:15–22 [View Article] [PubMed]
    [Google Scholar]
  38. Becker K, Schaumburg F, Kearns A, Larsen AR, Lindsay JA et al. Implications of identifying the recently defined members of the Staphylococcus aureus complex S. argenteus and S. schweitzeri: a position paper of members of the ESCMID Study Group for Staphylococci and Staphylococcal Diseases (ESGS). Clin Microbiol Infect 2019; 25:1064–1070 [View Article]
    [Google Scholar]
  39. 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] [PubMed]
    [Google Scholar]
  40. Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat Methods 2017; 14:587–589 [View Article] [PubMed]
    [Google Scholar]
  41. 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:W242–5 [View Article] [PubMed]
    [Google Scholar]
  42. Jolley KA, Maiden MCJ. BIGSdb: Scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics 2010; 11:595 [View Article] [PubMed]
    [Google Scholar]
  43. Oliveros J. 2007-2015. Venny. An interactive tool for comparing lists with Venn’s diagrams 2017 https://bioinfogp.cnb.csic.es/tools/venny/index.html
  44. Bertelli C, Laird MR, Williams KP. Simon Fraser University Research Computing Group Lau BY et al. IslandViewer 4: expanded prediction of genomic islands for larger-scale datasets. Nucleic Acids Res 2017; 45:W30–W35 [View Article] [PubMed]
    [Google Scholar]
  45. Johnson M, Zaretskaya I, Raytselis Y, Merezhuk Y, McGinnis S et al. NCBI BLAST: a better web interface. Nucleic Acids Res 2008; 36:W5–9 [View Article] [PubMed]
    [Google Scholar]
  46. Liu B, Zheng D, Jin Q, Chen L, Yang J. VFDB 2019: a comparative pathogenomic platform with an interactive web interface. Nucleic Acids Res 2019; 47:D687–D692 [View Article] [PubMed]
    [Google Scholar]
  47. Lakin SM, Dean C, Noyes NR, Dettenwanger A, Ross AS et al. MEGARes: an antimicrobial resistance database for high throughput sequencing. Nucleic Acids Res 2017; 45:D574–D580 [View Article] [PubMed]
    [Google Scholar]
  48. Roberts RJ, Vincze T, Posfai J, Macelis D. REBASE--a database for DNA restriction and modification: enzymes, genes and genomes. Nucleic Acids Res 2015; 43:D298–9 [View Article] [PubMed]
    [Google Scholar]
  49. Wang B, Muir TW. Regulation of virulence in Staphylococcus aureus: molecular mechanisms and remaining puzzles. Cell Chem Biol 2016; 23:214–224 [View Article] [PubMed]
    [Google Scholar]
  50. 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] [PubMed]
    [Google Scholar]
  51. Arndt D, Grant JR, Marcu A, Sajed T, Pon A et al. PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res 2016; 44:W16–21 [View Article]
    [Google Scholar]
  52. Setubal JC, Almeida NF, Wattam AR. Comparative genomics for prokaryotes. Methods Mol Biol 2018; 1704:55–78
    [Google Scholar]
  53. Bosi E, Monk JM, Aziz RK, Fondi M, Nizet V et al. Comparative genome-scale modelling of Staphylococcus aureus strains identifies strain-specific metabolic capabilities linked to pathogenicity. Proc Natl Acad Sci U S A 2016; 113:E3801–9 [View Article] [PubMed]
    [Google Scholar]
  54. Kozytska S, Stauss D, Pawlik M-C, Hensen S, Eckart M et al. Identification of specific genes in Staphylococcus aureus strains associated with bovine mastitis. Vet Microbiol 2010; 145:360–365 [View Article]
    [Google Scholar]
  55. 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]
  56. Resch G, François P, Morisset D, Stojanov M, Bonetti EJ et al. Human-to-bovine jump of Staphylococcus aureus CC8 is associated with the loss of a β-hemolysin converting prophage and the acquisition of a new staphylococcal cassette chromosome. PLoS One 2013; 8:e58187 [View Article] [PubMed]
    [Google Scholar]
  57. Spoor LE, McAdam PR, Weinert LA, Rambaut A, Hasman H et al. Livestock origin for a human pandemic clone of community-associated methicillin-resistant Staphylococcus aureus. mBio 2013; 4:e00356-13 [View Article] [PubMed]
    [Google Scholar]
  58. Jia H, Dong W, Yuan L, Ma J, Bai Q et al. Characterization and complete genome sequence analysis of Staphylococcus aureus bacteriophage JS01. Virus Genes 2015; 50:345–348 [View Article] [PubMed]
    [Google Scholar]
  59. McClure J-AM, Lakhundi S, Kashif A, Conly JM, Zhang K. Genomic comparison of highly virulent, moderately virulent, and avirulent strains from a genetically closely-related MRSA ST239 sub-lineage provides insights into pathogenesis. Front Microbiol 2018; 9:1531 [View Article] [PubMed]
    [Google Scholar]
  60. Park S, Classen A, Gohou HM, Maldonado R, Kretschmann E et al. A new, reliable, and high-throughput strategy to screen bacteria for antagonistic activity against Staphylococcus aureus. BMC Microbiol 2021; 21:189 [View Article] [PubMed]
    [Google Scholar]
  61. Nair D, Memmi G, Hernandez D, Bard J, Beaume M et al. Whole-genome sequencing of Staphylococcus aureus strain RN4220, a key laboratory strain used in virulence research, identifies mutations that affect not only virulence factors but also the fitness of the strain. J Bacteriol 2011; 193:2332–2335 [View Article] [PubMed]
    [Google Scholar]
  62. Wilson GJ, Tuffs SW, Wee BA, Seo KS, Park N et al. Bovine Staphylococcus aureus superantigens stimulate the entire T cell repertoire of cattle. Infect Immun 2018; 86:11 [View Article] [PubMed]
    [Google Scholar]
  63. Veiga H, Pinho MG. Inactivation of the SauI type I restriction-modification system is not sufficient to generate Staphylococcus aureus strains capable of efficiently accepting foreign DNA. Appl Environ Microbiol 2009; 75:3034–3038 [View Article] [PubMed]
    [Google Scholar]
  64. Moller AG, Lindsay JA, Read TD. Determinants of phage host range in Staphylococcus Species. Appl Environ Microbiol 2019; 85:11 [View Article] [PubMed]
    [Google Scholar]
  65. Ubeda C, Maiques E, Knecht E, Lasa I, Novick RP et al. Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci. Mol Microbiol 2005; 56:836–844 [View Article] [PubMed]
    [Google Scholar]
  66. Oliveira CJB, Tiao N, de Sousa FGC, de Moura JFP, Santos Filho L et al. Methicillin-resistant Staphylococcus aureus from Brazilian dairy farms and identification of novel sequence types. Zoonoses Public Health 2016; 63:97–105 [View Article] [PubMed]
    [Google Scholar]
  67. Feltrin F, Alba P, Kraushaar B, Ianzano A, Argudín MA et al. A livestock-associated, multidrug-resistant, methicillin-resistant Staphylococcus aureus clonal complex 97 lineage spreading in dairy cattle and pigs in Italy. Appl Environ Microbiol 2016; 82:816–821 [View Article] [PubMed]
    [Google Scholar]
  68. Cormican P, Keane OM. Complete genome sequences of sequence type 71 (ST71) and ST97 Staphylococcus aureus isolates from bovine milk. Microbiol Resour Announc 2018; 7:e00954-18 [View Article] [PubMed]
    [Google Scholar]
  69. Salustiano Marques-Bastos SL, Varella Coelho ML, Ceotto-Vigoder H, Carlin Fagundes P, Silva Almeida G et al. Molecular characterization of aureocin 4181: a natural N-formylated aureocin A70 variant with a broad spectrum of activity. Braz J Microbiol 2020; 51:1527–1538 [View Article] [PubMed]
    [Google Scholar]
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