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MRSA epidemic linked to a quickly spreading colonization and virulence determinant

Nature Medicine volume 18, pages 816–819 (2012)Cite this article

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Abstract

The molecular processes underlying epidemic waves of methicillin-resistant Staphylococcus aureus (MRSA) infection are poorly understood1. Although a major role has been attributed to the acquisition of virulence determinants by horizontal gene transfer2, there are insufficient epidemiological and functional data supporting that concept. We here report the spread of clones containing a previously extremely rare3,4 mobile genetic element–encoded gene, sasX. We demonstrate that sasX has a key role in MRSA colonization and pathogenesis, substantially enhancing nasal colonization, lung disease and abscess formation and promoting mechanisms of immune evasion. Moreover, we observed the recent spread of sasX from sequence type 239 (ST239) to invasive clones belonging to other sequence types. Our study identifies sasX as a quickly spreading crucial determinant of MRSA pathogenic success and a promising target for therapeutic interference. Our results provide proof of principle that horizontal gene transfer of key virulence determinants drives MRSA epidemic waves.

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Figure 1: Spread of sasX-positive clones in China.
Figure 2: The SasX surface protein facilitates nasal colonization.
Figure 3: SasX promotes bacterial aggregation and mechanisms of immune evasion.
Figure 4: SasX is a key virulence determinant during MRSA skin and lung infection.

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Acknowledgements

This study was supported by a grant from the China National Clinical Key Subject to Y.L., the National Natural Science Foundation of China (grants 30900026 and 81171623) and the Shanghai Pujiang Program (grant 09PJ1402300) to M.L., and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, US National Institutes of Health (to M.O.).

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Author notes

  1. Min Li and Xin Du: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Laboratory Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China

    Min Li, Xin Du, Yan Song, Yueru Tian, Jinhui Hu & Yuan Lu

  2. Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA

    Amer E Villaruz & Michael Otto

  3. Division of Infectious Diseases, Department of Medicine, University of California–San Francisco, San Francisco, California, USA

    Binh An Diep

  4. Key Laboratory of Medical Molecular Virology, Institutes of Medical Microbiology and Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China

    Decheng Wang

  5. Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China

    Fangyou Yu

Authors
  1. Min Li
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Contributions

M.L., X.D., A.E.V., D.W., Y.S., Y.T., J.H. and F.Y. conducted experiments. M.L., B.A.D., Y.L. and M.O. planned and supervised experiments. M.O. wrote the paper.

Corresponding authors

Correspondence to Yuan Lu or Michael Otto.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7, Supplementary Tables 1–3 and Supplementary Methods (PDF 1158 kb)

Supplementary Data

Characteristics of isolates investigated in this study (XLS 195 kb)

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Li, M., Du, X., Villaruz, A. et al. MRSA epidemic linked to a quickly spreading colonization and virulence determinant. Nat Med 18, 816–819 (2012). https://doi.org/10.1038/nm.2692

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