Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Staphylococcus aureus host interactions and adaptation

Nature Reviews Microbiology volume 21, pages 380–395 (2023)Cite this article

Subjects

Abstract

Invasive Staphylococcus aureus infections are common, causing high mortality, compounded by the propensity of the bacterium to develop drug resistance. S. aureus is an excellent case study of the potential for a bacterium to be commensal, colonizing, latent or disease-causing; these states defined by the interplay between S. aureus and host. This interplay is multidimensional and evolving, exemplified by the spread of S. aureus between humans and other animal reservoirs and the lack of success in vaccine development. In this Review, we examine recent advances in understanding the S. aureus–host interactions that lead to infections. We revisit the primary role of neutrophils in controlling infection, summarizing the discovery of new immune evasion molecules and the discovery of new functions ascribed to well-known virulence factors. We explore the intriguing intersection of bacterial and host metabolism, where crosstalk in both directions can influence immune responses and infection outcomes. This Review also assesses the surprising genomic plasticity of S. aureus, its dualism as a multi-mammalian species commensal and opportunistic pathogen and our developing understanding of the roles of other bacteria in shaping S. aureus colonization.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: New insights into Staphylococcus aureus immune evasion.
Fig. 2: Evasion of immunoglobulin and complement-mediated immunity.
Fig. 3: Staphylococcus aureus biofilm shapes the phenotype of leukocytes.
Fig. 4: Staphylococcus aureus host species adaptation over time.

Similar content being viewed by others

References

  1. Lowy, F. D. Staphylococcus aureus infections. N. Engl. J. Med. 339, 520–532 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Wertheim, H. F. et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect. Dis. 5, 751–762 (2005).

    Article  PubMed  Google Scholar 

  3. Williams, R. E. Healthy carriage of Staphylococcus aureus: its prevalence and importance. Bacteriol. Rev. 27, 56–71 (1963).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Krismer, B., Weidenmaier, C., Zipperer, A. & Peschel, A. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat. Rev. Microbiol. 15, 675–687 (2017). Excellent review on the nasal microbiome and the interaction with S. aureus.

    Article  CAS  PubMed  Google Scholar 

  5. Clarridge, J. E. III, Harrington, A. T., Roberts, M. C., Soge, O. O. & Maquelin, K. Impact of strain typing methods on assessment of relationship between paired nares and wound isolates of methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol. 51, 224–231 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Raineri, E. J. M., Altulea, D. & van Dijl, J. M. Staphylococcal trafficking and infection-from ‘nose to gut’ and back. FEMS Microbiol. Rev. 46, fuab041 (2022).

    Article  CAS  PubMed  Google Scholar 

  7. Spaan, A. N., van Strijp, J. A. G. & Torres, V. J. Leukocidins: staphylococcal bi-component pore-forming toxins find their receptors. Nat. Rev. Microbiol. 15, 435–447 (2017). Comprehensive review of the staphylococcal leukocidins.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Thammavongsa, V., Kim, H. K., Missiakas, D. & Schneewind, O. Staphylococcal manipulation of host immune responses. Nat. Rev. Microbiol. 13, 529–543 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Montgomery, C. P., David, M. Z. & Daum, R. S. Host factors that contribute to recurrent staphylococcal skin infection. Curr. Opin. Infect. Dis. 28, 253–258 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kallen, A. J. et al. Health care-associated invasive MRSA infections, 2005–2008. JAMA 304, 641–648 (2010).

    Article  CAS  PubMed  Google Scholar 

  11. Jansen, K. U., Girgenti, D. Q., Scully, I. L. & Anderson, A. S. Vaccine review: ‘Staphyloccocus aureus vaccines: problems and prospects’. Vaccine 31, 2723–2730 (2013).

    Article  CAS  PubMed  Google Scholar 

  12. Wollenberg, M. S. et al. Propionibacterium-produced coproporphyrin III induces Staphylococcus aureus aggregation and biofilm formation. mBio 5, e01286-14 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Costello, E. K. et al. Bacterial community variation in human body habitats across space and time. Science 326, 1694–1697 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Torres Salazar, B. O., Heilbronner, S., Peschel, A. & Krismer, B. Secondary metabolites governing microbiome interaction of Staphylococcal pathogens and commensals. Micro. Physiol. 31, 198–216 (2021).

    Article  Google Scholar 

  15. Lister, J. L. & Horswill, A. R. Staphylococcus aureus biofilms: recent developments in biofilm dispersal. Front. Cell Infect. Microbiol. 4, 178 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Archer, N. K. et al. Staphylococcus aureus biofilms: properties, regulation, and roles in human disease. Virulence 2, 445–459 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bhattacharya, M. et al. Staphylococcus aureus biofilms release leukocidins to elicit extracellular trap formation and evade neutrophil-mediated killing. Proc. Natl Acad. Sci. USA 115, 7416–7421 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chambers, H. F. & Deleo, F. R. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat. Rev. Microbiol. 7, 629–641 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Turner, N. A. et al. Methicillin-resistant Staphylococcus aureus: an overview of basic and clinical research. Nat. Rev. Microbiol. 17, 203–218 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Howden, B. P., Davies, J. K., Johnson, P. D., Stinear, T. P. & Grayson, M. L. Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin. Microbiol. Rev. 23, 99–139 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gao, W. et al. The RpoB H481Y rifampicin resistance mutation and an active stringent response reduce virulence and increase resistance to innate immune responses in Staphylococcus aureus. J. Infect. Dis. 207, 929–939 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Proctor, R. A. et al. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat. Rev. Microbiol. 4, 295–305 (2006).

    Article  CAS  PubMed  Google Scholar 

  23. Moller, A. G., Petit, R. A. III & Read, T. D. Species-scale genomic analysis of Staphylococcus aureus genes influencing phage host range and their relationships to virulence and antibiotic resistance genes. mSystems 7, e0108321 (2022).

    Article  PubMed  Google Scholar 

  24. Howden, B. P. et al. Evolution of multidrug resistance during Staphylococcus aureus infection involves mutation of the essential two component regulator WalKR. PLoS Pathog. 7, e1002359 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mwangi, M. M. et al. Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing. Proc. Natl Acad. Sci. USA 104, 9451–9456 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gao, W. et al. Large tandem chromosome expansions facilitate niche adaptation during persistent infection with drug-resistant Staphylococcus aureus. Microb. Genom. 1, e000026 (2015).

    PubMed  PubMed Central  Google Scholar 

  27. Panton, P. N. & Valentine, F. C. O. Staphylococcal toxin. Lancet 219, 506–508 (1932).

    Article  Google Scholar 

  28. Cheung, G. Y. C., Bae, J. S. & Otto, M. Pathogenicity and virulence of Staphylococcus aureus. Virulence 12, 547–569 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Curnutte, J. T., Whitten, D. M. & Babior, B. M. Defective superoxide production by granulocytes from patients with chronic granulomatous disease. N. Engl. J. Med. 290, 593–597 (1974).

    Article  CAS  PubMed  Google Scholar 

  30. Spaan, A. N., Surewaard, B. G., Nijland, R. & van Strijp, J. A. Neutrophils versus Staphylococcus aureus: a biological tug of war. Annu. Rev. Microbiol. 67, 629–650 (2013).

    Article  CAS  PubMed  Google Scholar 

  31. Stapels, D. A. et al. Staphylococcus aureus secretes a unique class of neutrophil serine protease inhibitors. Proc. Natl Acad. Sci. USA 111, 13187–13192 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kretschmer, D. et al. Staphylococcus aureus depends on eap proteins for preventing degradation of its phenol-soluble modulin toxins by neutrophil serine proteases. Front. Immunol. 12, 701093 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Stapels, D. A. et al. Staphylococcus aureus protects its immune-evasion proteins against degradation by neutrophil serine proteases. Cell Microbiol. 18, 536–545 (2016).

    Article  CAS  PubMed  Google Scholar 

  34. Ploscariu, N. T., de Jong, N. W. M., van Kessel, K. P. M., van Strijp, J. A. G. & Geisbrecht, B. V. Identification and structural characterization of a novel myeloperoxidase inhibitor from Staphylococcus delphini. Arch. Biochem. Biophys. 645, 1–11 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. de Jong, N. W. M. et al. Immune evasion by a staphylococcal inhibitor of myeloperoxidase. Proc. Natl Acad. Sci. USA 114, 9439–9444 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Loffler, B. et al. Staphylococcus aureus Panton-Valentine leukocidin is a very potent cytotoxic factor for human neutrophils. PloS Pathog. 6, e1000715 (2010).

    Article  PubMed Central  Google Scholar 

  37. Vrieling, M. et al. Population analysis of Staphylococcus aureus reveals a cryptic, highly prevalent superantigen SelW that contributes to the pathogenesis of bacteremia. mBio 11, e02082-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Wilson, G. J. et al. A novel core genome-encoded superantigen contributes to lethality of community-associated MRSA necrotizing pneumonia. PloS Pathog. 7, e1002271 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tuffs, S. W. et al. The Staphylococcus aureus superantigen SelX is a bifunctional toxin that inhibits neutrophil function. PloS Pathog. 13, e1006461 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Foster, T. J., Geoghegan, J. A., Ganesh, V. K. & Hook, M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat. Rev. Microbiol. 12, 49–62 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Corrigan, R. M., Miajlovic, H. & Foster, T. J. Surface proteins that promote adherence of Staphylococcus aureus to human desquamated nasal epithelial cells. BMC Microbiol. 9, 22 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Cheng, A. G. et al. Genetic requirements for Staphylococcus aureus abscess formation and persistence in host tissues. FASEB J. 23, 3393–3404 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Askarian, F. et al. Serine-aspartate repeat protein D increases Staphylococcus aureus virulence and survival in blood. Infect. Immun. 85, e00559-16 (2017).

    Article  PubMed  Google Scholar 

  44. Zhang, Y. et al. Staphylococcus aureus SdrE captures complement factor H’s C-terminus via a novel ‘close, dock, lock and latch’ mechanism for complement evasion. Biochem. J. 474, 1619–1631 (2017).

    Article  CAS  PubMed  Google Scholar 

  45. Speziale, P. & Pietrocola, G. The multivalent role of fibronectin-binding proteins A and B (FnBPA and FnBPB) of Staphylococcus aureus in host infections. Front. Microbiol. 11, 2054 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Pietrocola, G. et al. Fibronectin-binding protein B (FnBPB) from Staphylococcus aureus protects against the antimicrobial activity of histones. J. Biol. Chem. 294, 3588–3602 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Thammavongsa, V., Missiakas, D. M. & Schneewind, O. Staphylococcus aureus degrades neutrophil extracellular traps to promote immune cell death. Science 342, 863–866 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Soh, K. Y., Loh, J. M. S. & Proft, T. Cell wall-anchored 5ʹ-nucleotidases in Gram-positive cocci. Mol. Microbiol. 113, 691–698 (2020).

    Article  CAS  PubMed  Google Scholar 

  49. Berends, E. T. M. et al. Staphylococcus aureus impairs the function of and kills human dendritic cells via the LukAB toxin. mBio 10, e01918-18 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Badarau, A., Trstenjak, N. & Nagy, E. Structure and function of the two-component cytotoxins of Staphylococcus aureus — learnings for designing novel therapeutics. Adv. Exp. Med. Biol. 966, 15–35 (2017).

    Article  CAS  PubMed  Google Scholar 

  51. Perelman, S. S. et al. Genetic variation of staphylococcal LukAB toxin determines receptor tropism. Nat. Microbiol. 6, 731–745 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Spaan, A. N. et al. The staphylococcal toxin Panton-Valentine leukocidin targets human C5a receptors. Cell Host Microbe 13, 584–594 (2013).

    Article  CAS  PubMed  Google Scholar 

  53. Haapasalo, K. et al. Staphylococcus aureus toxin LukSF dissociates from its membrane receptor target to enable renewed ligand sequestration. FASEB J. 33, 3807–3824 (2019).

    Article  CAS  PubMed  Google Scholar 

  54. Tromp, A. T. et al. Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin. Nat. Microbiol. 3, 708–717 (2018).

    Article  CAS  PubMed  Google Scholar 

  55. Knop, J. et al. Staphylococcus aureus infection in humanized mice: a new model to study pathogenicity associated with human immune response. J. Infect. Dis. 212, 435–444 (2015).

    Article  CAS  PubMed  Google Scholar 

  56. Prince, A., Wang, H., Kitur, K. & Parker, D. Humanized mice exhibit increased susceptibility to Staphylococcus aureus pneumonia. J. Infect. Dis. 215, 1386–1395 (2017).

    CAS  PubMed  Google Scholar 

  57. Tseng, C. W. et al. Increased susceptibility of humanized NSG mice to Panton-Valentine leukocidin and Staphylococcus aureus skin infection. PLoS Pathog. 11, e1005292 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Muthukrishnan, G. et al. Humanized mice exhibit exacerbated abscess formation and osteolysis during the establishment of implant-associated Staphylococcus aureus osteomyelitis. Front. Immunol. 12, 651515 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chow, S. H. et al. Targeting NLRP3 and staphylococcal pore-forming toxin receptors in human-induced pluripotent stem cell-derived macrophages. J. Leukoc. Biol. 108, 967–981 (2020).

    Article  CAS  PubMed  Google Scholar 

  60. Lees, J. A. & Bentley, S. D. Bacterial GWAS: not just gilding the lily. Nat. Rev. Microbiol. 14, 406 (2016).

    Article  CAS  PubMed  Google Scholar 

  61. Young, B. C. et al. Panton-Valentine leucocidin is the key determinant of Staphylococcus aureus pyomyositis in a bacterial GWAS. eLife 8, e42486 (2019). Statistical genomics study linking a S. aureus virulence factor to a clinical manifestation.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Koymans, K. J. et al. Staphylococcal superantigen-like protein 1 and 5 (SSL1 & SSL5) limit neutrophil chemotaxis and migration through MMP-inhibition. Int. J. Mol. Sci. 17, 1072 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Bestebroer, J. et al. Staphylococcal SSL5 inhibits leukocyte activation by chemokines and anaphylatoxins. Blood 113, 328–337 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Tang, A. et al. Staphylococcus aureus superantigen-like protein SSL1: a toxic protease. Pathogens 8, 2 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Koymans, K. J. et al. The TLR2 antagonist Staphylococcal superantigen-like protein 3 acts as a virulence factor to promote bacterial pathogenicity in vivo. J. Innate Immun. 9, 561–573 (2017).

    Article  CAS  PubMed  Google Scholar 

  66. Zhao, Y. et al. Staphylococcal superantigen-like protein 13 activates neutrophils via formyl peptide receptor 2. Cell Microbiol. 20, e12941 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Diebolder, C. A. et al. Complement is activated by IgG hexamers assembled at the cell surface. Science 343, 1260–1263 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Becker, S., Frankel, M. B., Schneewind, O. & Missiakas, D. Release of protein A from the cell wall of Staphylococcus aureus. Proc. Natl Acad. Sci. USA 111, 1574–1579 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. O’Halloran, D. P., Wynne, K. & Geoghegan, J. A. Protein A is released into the Staphylococcus aureus culture supernatant with an unprocessed sorting signal. Infect. Immun. 83, 1598–1609 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Falugi, F., Kim, H. K., Missiakas, D. M. & Schneewind, O. Role of protein A in the evasion of host adaptive immune responses by Staphylococcus aureus. mBio 4, e00575-13 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Cruz, A. R. et al. Staphylococcal protein A inhibits complement activation by interfering with IgG hexamer formation. Proc. Natl Acad. Sci. USA 118, e2016772118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Hong, X. et al. Staphylococcal protein A promotes colonization and immune evasion of the epidemic healthcare-associated MRSA ST239. Front. Microbiol. 7, 951 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Smith, E. J. et al. The immune evasion protein Sbi of Staphylococcus aureus occurs both extracellularly and anchored to the cell envelope by binding lipoteichoic acid. Mol. Microbiol. 83, 789–804 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Dunphy, R. W. et al. Staphylococcal complement evasion protein Sbi stabilises C3d dimers by inducing an N-terminal helix swap. Front. Immunol. 13, 892234 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Dasari, P. et al. The protease SplB of Staphylococcus aureus targets host complement components and inhibits complement-mediated bacterial opsonophagocytosis. J. Bacteriol. 204, e0018421 (2022).

    Article  PubMed  Google Scholar 

  76. Bhattacharya, M. et al. Leukocidins and the nuclease nuc prevent neutrophil-mediated killing of Staphylococcus aureus biofilms. Infect. Immun. 88, e00372-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Schilcher, K. & Horswill, A. R. Staphylococcal biofilm development: structure, regulation, and treatment strategies. Microbiol. Mol. Biol. Rev. 84, e00026-19 (2020). Comprehensive review of S. aureus biofilms.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Ricciardi, B. F. et al. Staphylococcus aureus evasion of host immunity in the setting of prosthetic joint infection: biofilm and beyond. Curr. Rev. Musculoskelet. Med. 11, 389–400 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Arciola, C. R., Campoccia, D. & Montanaro, L. Implant infections: adhesion, biofilm formation and immune evasion. Nat. Rev. Microbiol. 16, 397–409 (2018).

    Article  CAS  PubMed  Google Scholar 

  80. Heim, C. E., Vidlak, D. & Kielian, T. Interleukin-10 production by myeloid-derived suppressor cells contributes to bacterial persistence during Staphylococcus aureus orthopedic biofilm infection. J. Leukoc. Biol. 98, 1003–1013 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Heim, C. E. et al. IL-12 promotes myeloid-derived suppressor cell recruitment and bacterial persistence during Staphylococcus aureus orthopedic implant infection. J. Immunol. 194, 3861–3872 (2015).

    Article  CAS  PubMed  Google Scholar 

  82. Heim, C. E. et al. Myeloid-derived suppressor cells contribute to Staphylococcus aureus orthopedic biofilm infection. J. Immunol. 192, 3778–3792 (2014).

    Article  CAS  PubMed  Google Scholar 

  83. Heim, C. E., West, S. C., Ali, H. & Kielian, T. Heterogeneity of Ly6G(+) Ly6C(+) myeloid-derived suppressor cell infiltrates during Staphylococcus aureus biofilm infection. Infect. Immun. 86, e00684-18 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Yamada, K. J. et al. Monocyte metabolic reprogramming promotes pro-inflammatory activity and Staphylococcus aureus biofilm clearance. PLoS Pathog. 16, e1008354 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Gabrilovich, D. I. & Nagaraj, S. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9, 162–174 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. O’Neill, L. A., Kishton, R. J. & Rathmell, J. A guide to immunometabolism for immunologists. Nat. Rev. Immunol. 16, 553–565 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Tannahill, G. M. et al. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496, 238–242 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Lampropoulou, V. et al. Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab. 24, 158–166 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Hooftman, A. et al. The immunomodulatory metabolite itaconate modifies NLRP3 and inhibits inflammasome activation. Cell Metab. 32, 468–478.e7 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Qin, W. et al. S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate. Nat. Chem. Biol. 15, 983–991 (2019).

    Article  CAS  PubMed  Google Scholar 

  91. Heim, C. E. et al. Lactate production by Staphylococcus aureus biofilm inhibits HDAC11 to reprogramme the host immune response during persistent infection. Nat. Microbiol. 5, 1271–1284 (2020). Sophisticated host–pathogen study using at-scale transposon mutagenesis to reveal the role mechanism of S. aureus lactate in regulation of IL-10 expression.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Tomlinson, K. L. & Riquelme, S. A. Host–bacteria metabolic crosstalk drives S. aureus biofilm. Microb. Cell 8, 106–107 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Tomlinson, K. L. et al. Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation. Nat. Commun. 12, 1399 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Michelucci, A. et al. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc. Natl Acad. Sci. USA 110, 7820–7825 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Arts, R. J. et al. Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metab. 24, 807–819 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Chan, L. C. et al. Innate immune memory contributes to host defense against recurrent skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus. Infect. Immun. 85, e00876-16 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Chan, L. C. et al. Protective immunity in recurrent Staphylococcus aureus infection reflects localized immune signatures and macrophage-conferred memory. Proc. Natl Acad. Sci. USA 115, E11111–E11119 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Acker, K. P. et al. Strains of Staphylococcus aureus that colonize and infect skin harbor mutations in metabolic genes. iScience 19, 281–290 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Wong Fok Lung, T. et al. Staphylococcus aureus small colony variants impair host immunity by activating host cell glycolysis and inducing necroptosis. Nat. Microbiol. 5, 141–153 (2020).

    Article  CAS  PubMed  Google Scholar 

  100. Proctor, R. A., van Langevelde, P., Kristjansson, M., Maslow, J. N. & Arbeit, R. D. Persistent and relapsing infections associated with small-colony variants of Staphylococcus aureus. Clin. Infect. Dis. 20, 95–102 (1995).

    Article  CAS  PubMed  Google Scholar 

  101. Kriegeskorte, A. et al. Staphylococcus aureus small colony variants show common metabolic features in central metabolism irrespective of the underlying auxotrophism. Front. Cell Infect. Microbiol. 4, 141 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Gabryszewski, S. J. et al. Metabolic adaptation in methicillin-resistant Staphylococcus aureus pneumonia. Am. J. Respir. Cell Mol. Biol. 61, 185–197 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Guerillot, R. et al. Unstable chromosome rearrangements in Staphylococcus aureus cause phenotype switching associated with persistent infections. Proc. Natl Acad. Sci. USA 116, 20135–20140 (2019). Identification of a reversible genome rearrangement contributing to the SCV phenotype in S. aureus.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Richardson, E. J. et al. Gene exchange drives the ecological success of a multi-host bacterial pathogen. Nat. Ecol. Evol. 2, 1468–1478 (2018). Excellent demonstration of bacterial population genomics to reveal the extent to which humans are shaping the evolution of S. aureus and exchange between different animal hosts.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Price, L. B. et al. Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock. mBio 3, e00305-11 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Hau, S. J., Sun, J., Davies, P. R., Frana, T. S. & Nicholson, T. L. Comparative prevalence of immune evasion complex genes associated with beta-hemolysin converting bacteriophages in MRSA ST5 isolates from swine, swine facilities, humans with swine contact, and humans with no swine contact. PLoS ONE 10, e0142832 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Sahibzada, S. et al. Transmission of highly virulent community-associated MRSA ST93 and livestock-associated MRSA ST398 between humans and pigs in Australia. Sci. Rep. 7, 5273 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Spoor, L. E. et al. Livestock origin for a human pandemic clone of community-associated methicillin-resistant Staphylococcus aureus. mBio 4, e00356-13 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  109. Larsen, J. et al. Emergence of methicillin resistance predates the clinical use of antibiotics. Nature 602, 135–141 (2022). Large-scale genomic study identifying an animal source for antimicrobial-resistant S. aureus in humans.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Hallatschek, O., Hersen, P., Ramanathan, S. & Nelson, D. R. Genetic drift at expanding frontiers promotes gene segregation. Proc. Natl Acad. Sci. USA 104, 19926–19930 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Nei, M. Selectionism and neutralism in molecular evolution. Mol. Biol. Evol. 22, 2318–2342 (2005).

    Article  CAS  PubMed  Google Scholar 

  112. McVicker, G. et al. Clonal expansion during Staphylococcus aureus infection dynamics reveals the effect of antibiotic intervention. PLoS Pathog. 10, e1003959 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  113. Didelot, X., Walker, A. S., Peto, T. E., Crook, D. W. & Wilson, D. J. Within-host evolution of bacterial pathogens. Nat. Rev. Microbiol. 14, 150–162 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sheppard, S. K., Guttman, D. S. & Fitzgerald, J. R. Population genomics of bacterial host adaptation. Nat. Rev. Genet. 19, 549–565 (2018). Comprehensive review of bacterial host species adaptation.

    Article  CAS  PubMed  Google Scholar 

  115. Guinane, C. M. et al. Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation. Genome Biol. Evol. 2, 454–466 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Viana, D. et al. A single natural nucleotide mutation alters bacterial pathogen host tropism. Nat. Genet. 47, 361–366 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Bacigalupe, R., Tormo-Mas, M. A., Penades, J. R. & Fitzgerald, J. R. A multihost bacterial pathogen overcomes continuous population bottlenecks to adapt to new host species. Sci. Adv. 5, eaax0063 (2019). Experimental study demonstrating the capacity of S. aureus to acquire beneficial mutations alleviating evolutionary bottlenecks and enabling its adaptation to different hosts.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Zhou, W. et al. WGS analysis of ST9-MRSA-XII isolates from live pigs in China provides insights into transmission among porcine, human and bovine hosts. J. Antimicrob. Chemother. 73, 2652–2661 (2018).

    Article  CAS  PubMed  Google Scholar 

  119. Haag, A. F., Fitzgerald, J. R. & Penades, J. R. Staphylococcus aureus in animals. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.GPP3-0060-2019 (2019).

    Article  PubMed  Google Scholar 

  120. Vrieling, M. et al. Bovine Staphylococcus aureus secretes the leukocidin LukMF’ to kill migrating neutrophils through CCR1. mBio 6, e00335 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Matuszewska, M., Murray, G. G. R., Harrison, E. M., Holmes, M. A. & Weinert, L. A. The evolutionary genomics of host specificity in Staphylococcus aureus. Trends Microbiol. 28, 465–477 (2020).

    Article  CAS  PubMed  Google Scholar 

  122. Park, S. & Ronholm, J. Staphylococcus aureus in agriculture: lessons in evolution from a multispecies pathogen. Clin. Microbiol. Rev. 34, e00182-20 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  123. de Jong, N. W. M. et al. Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains. J. Biol. Chem. 293, 4468–4477 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Petit, R. A. III & Read, T. D. Staphylococcus aureus viewed from the perspective of 40,000+ genomes. Peer J. 6, e5261 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Lindsay, J. A. Genomic variation and evolution of Staphylococcus aureus. Int. J. Med. Microbiol. 300, 98–103 (2010).

    Article  CAS  PubMed  Google Scholar 

  126. Malachowa, N. & DeLeo, F. R. Mobile genetic elements of Staphylococcus aureus. Cell Mol. Life Sci. 67, 3057–3071 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Golubchik, T. et al. Within-host evolution of Staphylococcus aureus during asymptomatic carriage. PLoS ONE 8, e61319 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Everitt, R. G. et al. Mobile elements drive recombination hotspots in the core genome of Staphylococcus aureus. Nat. Commun. 5, 3956 (2014).

    Article  CAS  PubMed  Google Scholar 

  129. Prunier, A.-L. et al. High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains. J. Infect. Dis. 187, 1709–1716 (2003).

    Article  CAS  PubMed  Google Scholar 

  130. Giulieri, S. G. et al. Niche-specific genome degradation and convergent evolution shaping Staphylococcus aureus adaptation during severe infections. eLife 11, e77195 (2022). Population genomics conducted on a very large clinical cohort to reveal with unprecedented resolution the bacterial genome-wide changes that are associated with the transition from colonizing to invasive S. aureus infections.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Giulieri, S. G. et al. Genomic exploration of sequential clinical isolates reveals a distinctive molecular signature of persistent Staphylococcus aureus bacteraemia. Genome Med. 10, 65 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Klemm, E. J. et al. Emergence of host-adapted Salmonella Enteritidis through rapid evolution in an immunocompromised host. Nat. Microbiol. 1, 15023 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Batut, B., Knibbe, C., Marais, G. & Daubin, V. Reductive genome evolution at both ends of the bacterial population size spectrum. Nat. Rev. Microbiol. 12, 841–850 (2014).

    Article  CAS  PubMed  Google Scholar 

  134. Hall, M. D. et al. Improved characterisation of MRSA transmission using within-host bacterial sequence diversity. eLife 8, 46402 (2019).

    Article  Google Scholar 

  135. Long, D. R. et al. Polyclonality, shared strains, and convergent evolution in chronic CF S. aureus airway infection. Am. J. Respir. Crit. Care Med. 203, 1127–1137 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Young, B. C. et al. Evolutionary dynamics of Staphylococcus aureus during progression from carriage to disease. Proc. Natl Acad. Sci. USA 109, 4550–4555 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Young, B. C. et al. Severe infections emerge from commensal bacteria by adaptive evolution. eLife 6, e30637 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Altman, D. R. et al. Genome plasticity of agr-defective Staphylococcus aureus during clinical infection. Infect. Immun. 86, e00331-18 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Das, S. et al. Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation. Proc. Natl Acad. Sci. USA 113, E3101–E3110 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Paudel, A., Panthee, S., Hamamoto, H., Grunert, T. & Sekimizu, K. YjbH regulates virulence genes expression and oxidative stress resistance in Staphylococcus aureus. Virulence 12, 470–480 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Jousselin, A., Kelley, W. L., Barras, C., Lew, D. P. & Renzoni, A. The Staphylococcus aureus Thiol/oxidative stress global regulator Spx controls trfA, a gene implicated in cell wall antibiotic resistance. Antimicrob. Agents Chemother. 57, 3283–3292 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Lopatkin, A. J. et al. Clinically relevant mutations in core metabolic genes confer antibiotic resistance. Science 371, eaba0862 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Elgrail, M. M. et al. Convergent evolution of antibiotic tolerance in patients with persistent methicillin-resistant Staphylococcus aureus bacteremia. Infect. Immun. 90, e0000122 (2022).

    Article  PubMed  Google Scholar 

  144. Giulieri, S. G. et al. Comprehensive genomic investigation of adaptive mutations driving the low-level oxacillin resistance phenotype in Staphylococcus aureus. mBio 11, e02882-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Howden, B. P., Johnson, P. D., Ward, P. B., Stinear, T. P. & Davies, J. K. Isolates with low-level vancomycin resistance associated with persistent methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob. Agents Chemother. 50, 3039–3047 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Loss, G. et al. Staphylococcus aureus small colony variants (SCVs): news from a chronic prosthetic joint infection. Front. Cell Infect. Microbiol. 9, 363 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Bär, J. et al. Quantification of within-patient Staphylococcus aureus phenotypic heterogeneity as a proxy for presence of persisters across clinical presentations. Clin. Microbiol. Infect. 28, 1022.e1–1022.e7 (2022).

    Article  PubMed  Google Scholar 

  148. Laabei, M. et al. Evolutionary trade-offs underlie the multi-faceted virulence of Staphylococcus aureus. PLoS Biol. 13, e1002229 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Xiong, Y. Q. et al. Phenotypic and genotypic characteristics of persistent methicillin-resistant Staphylococcus aureus bacteremia in vitro and in an experimental endocarditis model. J. Infect. Dis. 199, 201–208 (2009).

    Article  CAS  PubMed  Google Scholar 

  150. Scott, W. K. et al. Human genetic variation in GLS2 is associated with development of complicated Staphylococcus aureus bacteremia. PLoS Genet. 14, e1007667 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Spaan, A. N. et al. Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal alpha-toxin. Science 376, eabm6380 (2022). This is the first evidence of a human heterozygous gene deficiency predisposing patients to severe S. aureus infection.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Chang, Y. L. et al. Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia. Proc. Natl Acad. Sci. USA 118, e2000663118 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Ford, C. A., Hurford, I. M. & Cassat, J. E. Antivirulence strategies for the treatment of Staphylococcus aureus infections: a mini review. Front. Microbiol. 11, 632706 (2020).

    Article  PubMed  Google Scholar 

  154. Francois, B. et al. Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial. Intensive Care Med. 44, 1787–1796 (2018).

    Article  CAS  PubMed  Google Scholar 

  155. Magyarics, Z. et al. Randomized, double-blind, placebo-controlled, single-ascending-dose study of the penetration of a monoclonal antibody combination (ASN100) targeting Staphylococcus aureus cytotoxins in the lung epithelial lining fluid of healthy volunteers. Antimicrob. Agents Chemother. 63, e00350-19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Chan, R. et al. Identification of biologic agents to neutralize the bicomponent leukocidins of Staphylococcus aureus. Sci. Transl Med. 11, eaat0882 (2019).

    Article  CAS  PubMed  Google Scholar 

  157. Mansson, M. et al. Inhibition of virulence gene expression in Staphylococcus aureus by novel depsipeptides from a marine photobacterium. Mar. Drugs 9, 2537–2552 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Gao, P., Davies, J. & Kao, R. Y. T. Dehydrosqualene desaturase as a novel target for anti-virulence therapy against Staphylococcus aureus. mBio 8, e01224-17 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  159. Chen, X., Schneewind, O. & Missiakas, D. Engineered human antibodies for the opsonization and killing of Staphylococcus aureus. Proc. Natl Acad. Sci. USA 119, e2114478119 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Miller, L. S., Fowler, V. G., Shukla, S. K., Rose, W. E. & Proctor, R. A. Development of a vaccine against Staphylococcus aureus invasive infections: evidence based on human immunity, genetics and bacterial evasion mechanisms. FEMS Microbiol. Rev. 44, 123–153 (2020).

    Article  CAS  PubMed  Google Scholar 

  161. Tsai, C. M. et al. Non-protective immune imprint underlies failure of Staphylococcus aureus IsdB vaccine. Cell Host Microbe 30, 1163–1172 (2022).

    Article  CAS  PubMed  Google Scholar 

  162. Nakatsuji, T. et al. Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial. Nat. Med. 27, 700–709 (2021). Clinical study of bacteriotherapy highlighting that the inhibition of PSM production by commensal S. hominis decreases S. aureus colonization in atopic dermatitis patients.

    Article  CAS  PubMed  Google Scholar 

  163. Liu, Y. et al. Skin microbiota analysis-inspired development of novel anti-infectives. Microbiome 8, 85 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Piewngam, P. & Otto, M. Probiotics to prevent Staphylococcus aureus disease? Gut Microbes 11, 94–101 (2020).

    Article  CAS  PubMed  Google Scholar 

  165. Olagnier, D. et al. SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate. Nat. Commun. 11, 4938 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Horn, C. M. & Kielian, T. Crosstalk between Staphylococcus aureus and innate immunity: focus on immunometabolism. Front. Immunol. 11, 621750 (2020).

    Article  CAS  PubMed  Google Scholar 

  167. Prince, A. & Wong Fok Lung, T. Consequences of metabolic interactions during Staphylococcus aureus infection. Toxins 12, 581 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  168. Thurlow, L. R. et al. Staphylococcus aureus biofilms prevent macrophage phagocytosis and attenuate inflammation in vivo. J. Immunol. 186, 6585–6596 (2011).

    Article  CAS  PubMed  Google Scholar 

  169. Pleasance, E. et al. Whole genome and transcriptome analysis enhances precision cancer treatment options. Ann. Oncol. 33, 939–949 (2022).

    Article  CAS  PubMed  Google Scholar 

  170. Recker, M. et al. Clonal differences in Staphylococcus aureus bacteraemia-associated mortality. Nat. Microbiol. 2, 1381–1388 (2017).

    Article  CAS  PubMed  Google Scholar 

  171. Young, B. C. et al. Antimicrobial resistance determinants are associated with Staphylococcus aureus bacteraemia and adaptation to the healthcare environment: a bacterial genome-wide association study. Microb. Genom. 7, 000700 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Lilje, B. et al. Whole-genome sequencing of bloodstream Staphylococcus aureus isolates does not distinguish bacteraemia from endocarditis. Microb. Genom. https://doi.org/10.1099/mgen.0.000138 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Denamur, E. et al. Genome wide association study of Escherichia coli bloodstream infection isolates identifies genetic determinants for the portal of entry but not fatal outcome. PLoS Genet. 18, e1010112 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Wozniak, J. M. et al. Mortality risk profiling of Staphylococcus aureus bacteremia by multi-omic serum analysis reveals early predictive and pathogenic signatures. Cell 182, 1311–1327 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Health and Medical Research Council Australia through Investigator Grants to B.P.H. (GNT1196103) and T.P.S. (GNT1194325).

Author information

Authors and Affiliations

  1. Centre for Pathogen Genomics, The University of Melbourne, Melbourne, Victoria, Australia

    Benjamin P. Howden & Timothy P. Stinear

  2. Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

    Benjamin P. Howden, Stefano G. Giulieri, Sarah L. Baines, Liam K. Sharkey, Jean Y. H. Lee, Abderrahman Hachani, Ian R. Monk & Timothy P. Stinear

  3. Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia

    Benjamin P. Howden

  4. Microbiology Department, Royal Melbourne Hospital, Melbourne, Victoria, Australia

    Benjamin P. Howden

  5. Victorian Infectious Diseases Service, Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia

    Stefano G. Giulieri

  6. Department of Paediatrics, Columbia University, New York, NY, USA

    Tania Wong Fok Lung

  7. Department of Infectious Diseases, Monash Health, Clayton, Victoria, Australia

    Jean Y. H. Lee

Authors
  1. Benjamin P. Howden
    View author publications

    Search author on:PubMed Google Scholar

  2. Stefano G. Giulieri
    View author publications

    Search author on:PubMed Google Scholar

  3. Tania Wong Fok Lung
    View author publications

    Search author on:PubMed Google Scholar

  4. Sarah L. Baines
    View author publications

    Search author on:PubMed Google Scholar

  5. Liam K. Sharkey
    View author publications

    Search author on:PubMed Google Scholar

  6. Jean Y. H. Lee
    View author publications

    Search author on:PubMed Google Scholar

  7. Abderrahman Hachani
    View author publications

    Search author on:PubMed Google Scholar

  8. Ian R. Monk
    View author publications

    Search author on:PubMed Google Scholar

  9. Timothy P. Stinear
    View author publications

    Search author on:PubMed Google Scholar

Contributions

B.P.H., T.P.S., S.G.G., S.L.B., L.K.S., J.Y.H.L., A.H., I.R.M. and T.W.F.L. researched data for the article. B.P.H., T.P.S., S.G.G., S.L.B., J.Y.H.L., A.H., I.R.M. and T.W.F.L. substantially contributed to discussion of content. B.P.H. and T.P.S. led the writing of the article with contributions from S.G.G., J.Y.H.L., A.H., I.R.M. and T.W.F.L. B.P.H., T.P.S., S.G.G., L.K.S., A.H., I.R.M. and T.W.F.L. reviewed and edited the article.

Corresponding author

Correspondence to Benjamin P. Howden.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Microbiology thanks Jos van Strijp, Timothy Foster and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Glossary

Accessory genome

Genes usually associated with mobile genetic elements that are present in only a subset of S. aureus strains. The accessory genome is one cause of variability in strain behaviour.

Biofilms

A sessile microbial community usually enclosed by a protective extracellular matrix and attached to a surface or other cells.

Bottlenecks

When a population (for example, bacterial population) is significantly reduced in size, limiting genetic diversity.

Carbon catabolite repression

(CCR). A bacterial global regulatory process that results in the selective use of substrates from a mixture of carbon sources.

Chronic granulomatous diseases

Rare X-linked recessive inherited immune deficiencies caused by defects in the enzyme, NADPH oxidase resulting in phagocytic dysfunction.

Colonization

The presence of S. aureus on a body site such as the skin, gut or anterior nares, without causing disease.

Core genome

Represents genes that are present in all S. aureus strains.

Efferocytosis

A process of phagocytic engulfment of dead or dying cells.

Evasion

Strategies used by bacteria to evade killing by the immune system.

Genetic drift

A change in the frequency of an existing genetic variant in a population owing to random chance.

Genome-wide association studies

The use of statistical genomics methods to identify the genetic variants linked to a particular phenotype.

Insertion sequences

A short segment of DNA that can move within the S. aureus chromosome as a simple transposable element and contribute to bacterial adaptation.

Invasion

The ability of a bacterial pathogen to spread to other locations in the host by invading host cells, such as the transition from the anterior nares (colonization) to the bloodstream (invasion).

Leukotoxins

Toxin proteins that penetrate lipid bilayers to form pores.

Lipopolysaccharide

Important outer membrane component of Gram-negative bacterial cell walls that acts as an endotoxin.

Machine learning

The application of computer systems using statistical models and algorithms to draw conclusions from data.

Microbial surface components recognizing adhesive matrix molecules

(MSCRAMMs). Adhesin proteins that are important in the initial binding of S. aureus to host tissues.

Mobile genetic elements

Sequences of genetic material that can change places in the S. aureus chromosome or move between bacterial chromosomes.

Persistence

Broadly refers to the ability of bacterial cells, including S. aureus, to cause persistent infection, despite the activity of the immune system or antibiotic therapy.

Pyomyositis

Deep infection in the skeletal muscles, usually associated with abscess formation.

Recurrent

The propensity for S. aureus infection to recur after initial successful therapy through surgery and/or antibiotics.

Small colony variant

(SCV). A slow-growing (small colony) population of S. aureus that is associated with persistent and recurrent infections.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Howden, B.P., Giulieri, S.G., Wong Fok Lung, T. et al. Staphylococcus aureus host interactions and adaptation. Nat Rev Microbiol 21, 380–395 (2023). https://doi.org/10.1038/s41579-023-00852-y

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41579-023-00852-y

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology