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Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment

Nature Reviews Microbiology (2025)Cite this article

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Abstract

Staphylococcus aureus is capable of infecting every organ system in the body and developing resistance to every available antibiotic used to treat it, such as methicillin-resistant S. aureus (commonly referred to as MRSA). This pathogen is characterized by the sudden emergence of virulent new clones and an array of mechanisms to circumvent the immune system and antibiotics. Furthermore, despite the development of new antibiotics and a growing body of high-quality data to inform their use, S. aureus continues to be a leading bacterial cause of death worldwide. In this Review, we provide an overview of the basic research on the complex interplay between S. aureus, the host and antibiotics. We also provide an update on the contemporary clinical studies on the treatment and prevention of S. aureus.

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Fig. 1: Clinical manifestations of Staphylococcus aureus infection.
Fig. 2: Mechanisms of Staphylococcus aureus immune evasion.
Fig. 3: Examples of how Staphylococcus aureus elicits maladaptive immune programmes.
Fig. 4: Host phagocyte activity and biofilm formation induce antibiotic tolerance.

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Acknowledgements

The authors gratefully acknowledge R. McLoughlin (Trinity College Dublin, Ireland) for critical review of the immune aspects discussed in the manuscript and Z. Van Roy (University of Nebraska Medical Center, Omaha, USA) for assistance with generating Figs. 2 and 3.

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Joshua B. Parsons, Ahmad Mourad & Vance G. Fowler Jr

  2. Duke Clinical Research Institute, Duke University, Durham, NC, USA

    Ahmad Mourad & Vance G. Fowler Jr

  3. Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA

    Brian P. Conlon

  4. Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE, USA

    Tammy Kielian

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  1. Joshua B. Parsons
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  2. Ahmad Mourad
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  3. Brian P. Conlon
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  4. Tammy Kielian
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  5. Vance G. Fowler Jr
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The authors contributed equally to all aspects of the article.

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Correspondence to Vance G. Fowler Jr.

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Competing interests

In the past 2 years, V.G.F. reports receiving the research grants to his institution from the following sponsors: NIH, Merck, Contrafect, Karius, Basilea, Janssen, Astra Zeneca and EDE; receiving compensation as a Consultant from the following companies: Akagera, Astra Zeneca, Armata, Basilea, Debiopharm, GSK, Integrated Biotherapeutics; owning stock options in Valanbio; receiving Royalties from UpToDate; and partial ownership on patent pending sepsis diagnostic. The other authors declare no competing interests.

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Parsons, J.B., Mourad, A., Conlon, B.P. et al. Methicillin-resistant and susceptible Staphylococcus aureus: tolerance, immune evasion and treatment. Nat Rev Microbiol (2025). https://doi.org/10.1038/s41579-025-01226-2

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