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A synthetic peptide adhesion epitope as a novel antimicrobial agent

Nature Biotechnology volume 17, pages 42–47 (1999)Cite this article

Abstract

The earliest step in microbial infection is adherence by specific microbial adhesins to the mucosa of the oro-intestinal, nasorespiratory, or genitourinary tract. We inhibited binding of a cell surface adhesin of Streptococcus mutans to salivary receptors in vitro, as measured by surface plasmon resonance, using a synthetic peptide (p1025) corresponding to residues 1025–1044 of the adhesin. Two residues within p1025 that contribute to binding (Q1025, E1037) were identified by site-directed mutagenesis. In an in vivo human streptococcal adhesion model, direct application of p1025 to the teeth prevented recolonization of S. mutans but not Actinomyces , as compared with a control peptide or saline. This novel antimicrobial strategy, applying competitive peptide inhibitors of adhesion, may be used against other microorganisms in which adhesins mediate colonization of mucosal surfaces.

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Figure 1: Peptide-mediated inhibition of SA I/II binding to salivary agglutinin.
Figure 2: Effect of alanine substitutions on p1025-mediated inhibition of SA I/II binding to salivary agglutinin.
Figure 3: Binding kinetics of wild-type and mutagenized C-terminal fragments of SA I/II to salivary agglutinin.
Figure 4: Recolonization of S. mutans in the oral cavity in (A) dental plaque, (B) saliva, and (C) Actinomyces in dental plaque.
Figure 5: Persistence of p1025 in vivo.

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Acknowledgements

This work was supported by the Wellcome Trust grant 040412 and the Special Funds of Guy's Hospital Dental School. NMR spectroscopic studies were supported by the TMR program "Access to Large-Scale Facilities" of the EC (ERBFMGECT950032). The BIAcore facility was established with funds from the Special Trustees of Guy's Hospital and the Special Trustees for St. Thomas' Hospital.

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Authors and Affiliations

  1. Department of Immunology, St. John's Institute of Dermatology United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, SE1 9RT, UK

    Charles G. Kelly, Justine S. Younson, Ban Y. Hikmat, Stephen M. Todryk, Julian K-C. Ma & Thomas Lehner

  2. Department of Oral Medicine and Pathology, St. John's Institute of Dermatology, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, SE1 9RT, UK

    Charles G. Kelly, Justine S. Younson, Ban Y. Hikmat, Ian R. Flindall & Julian K-C. Ma

  3. St. John's Institute of Dermatology, United Medical and Dental Schools of Guy's and St. Thomas' Hospitals, London, SE1 9RT, UK

    Craig Newby & Anthony I. Mallet

  4. Bijvoet Center for Biomolecular Research, Utrecht University, The Netherlands

    Michael Czisch

  5. Department of Biological Sciences, De Montfort University, Leicester, UK

    Parvez I. Haris

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  1. Charles G. Kelly
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Correspondence to Charles G. Kelly.

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Kelly, C., Younson, J., Hikmat, B. et al. A synthetic peptide adhesion epitope as a novel antimicrobial agent. Nat Biotechnol 17, 42–47 (1999). https://doi.org/10.1038/5213

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