Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization

Abstract

Commensal bacteria are known to inhibit pathogen colonization; however, complex host–microbe and microbe–microbe interactions have made it difficult to gain a detailed understanding of the mechanisms involved in the inhibition of colonization1. Here we show that the serine protease Esp2,3 secreted by a subset of Staphylococcus epidermidis, a commensal bacterium, inhibits biofilm formation and nasal colonization by Staphylococcus aureus, a human pathogen4. Epidemiological studies have demonstrated that the presence of Esp-secreting S. epidermidis in the nasal cavities of human volunteers correlates with the absence of S. aureus. Purified Esp inhibits biofilm formation and destroys pre-existing S. aureus biofilms. Furthermore, Esp enhances the susceptibility of S. aureus in biofilms to immune system components. In vivo studies have shown that Esp-secreting S. epidermidis eliminates S. aureus nasal colonization. These findings indicate that Esp hinders S. aureus colonization in vivo through a novel mechanism of bacterial interference, which could lead to the development of novel therapeutics to prevent S. aureus colonization and infection.

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Figure 1: Inhibition of S. aureus biofilm formation and destruction of S. aureus biofilms by S. epidermidis.
Figure 2: Isolation and characterization of the serine protease Esp, the factor responsible for the biofilm-destruction activity, secreted by inhibitory S. epidermidis.
Figure 3: Elimination effect of inhibitory S. epidermidis cells on S. aureus nasal colonization.

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Acknowledgements

We thank K. Hiramatsu and T. Bae for providing materials and M. Sekiguchi, T. Bae, S. N. Wai, B. E. Uhlin, L. Cui, T. Ito, M. Yoneda, M. Urashima and S. Masuda for discussions, critical comments and advice. Thanks also go to S. Kuramoto, K. Seki, F. Sato, S. Hoshina, T. Ohashi, H. Ikeshima-Kataoka, Y. Yoshizawa, M. Murai and M. Kono for their comments on the study, and to J. Fitzpatrick and M. Okazaki for their comments on the manuscript, and to our colleagues for their assistance. Finally, we thank all persons involved in the study. A part of the study was supported by The Jikei University Research Fund and by The Jikei University Graduate Research Fund.

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T.I. and Y.M. designed the research and wrote the manuscript. All authors contributed the experiments; T.I., H.S., A.T., K.T. and Y.M. for in vitro study and epidemiological study, Y.U. and H.S. for in vivo study, T.A. for statistics. All authors discussed the results and commented on the manuscript.

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Correspondence to Tadayuki Iwase.

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Iwase, T., Uehara, Y., Shinji, H. et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature 465, 346–349 (2010). https://doi.org/10.1038/nature09074

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