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Fluorescence assay to predict activity of the glycopeptide antibiotics

The Journal of Antibiotics volume 72, pages 114–117 (2019)Cite this article

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Abstract

Here, we describe a fluorescent assay developed to study competitive binding of the glycopeptide antibiotics to live bacteria cells. This assay demonstrated that the mechanism of action of the lipoglycopeptide antibiotics strongly depends on the hydrophobicity of the substitutes, with the best antibacterial activity of the glycopeptide antibiotics equally sharing properties of binding to d-Ala–d-Ala residues of the nascent peptidoglycan and to the membrane.

For many years, vancomycin and teicoplanin were the only glycopeptide antibiotics used clinically in treatment of severe infections caused by gram-positive pathogens. However, the spread of glycopeptide-resistant enterococci and staphylococci has led to a renewed interest in the development of novel derivatives of the glycopeptide antibiotics [1,2,3]. Semisynthetic lipoglycopeptide antibiotics telavancin, dalbavancin and oritavancin, with improved antibacterial activity and pharmacokinetics in comparison to vancomycin and teicoplanin, were recently approved for clinical usage. The improved activity of these lipoglycopeptide antibiotics was associated with lipophilic substitutes introduced to glycopeptides, which enhanced interaction of the antibiotics with cell-wall precursors and with the membrane, leading to inhibition of cell wall synthesis, as well as disruption of cell membrane integrity [4,5,6]. Because of the complexity of the binding of glycopeptide antibiotics to the cell wall, involving binding to the terminal d-Ala–d-Ala residues of the nascent peptidoglycan, peptidoglycan bridges, interaction with the membrane and antibiotic dimerization [7], direct comparison of the efficiency of binding of different glycopeptide antibiotics to live bacterial cells was lacking.

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Acknowledgements

We thank Dr. M. Horsburgh for providing us with S. aureus strains from his collection. This work was supported by the Czech Health Research Council project NV15-28807A, by the project BIOCEV—Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University (CZ.1.05/1.1.00/02.010) from the European Regional Development Fund in the Czech Republic, and by the EU, and co-financed by the European Regional Development Fund under the project GINOP-2.3.2 – 15-2016-00008.

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Authors and Affiliations

  1. Institute of Microbiology v. v. i., Czech Academy of Sciences, Vestec, Czech Republic

    Vladimir Vimberg, Radek Gazak, Leona Zieglerova & Gabriela Balikova Novotna

  2. Department of Pharmaceutical Chemistry, University of Debrecen, Debrecen, Hungary

    Zsolt Szűcs, Aniko Borbás & Pal Herczegh

  3. Department of Pediatrics, University Hospital of North Norway, Tromsø, Norway

    Jorunn Pauline Cavanagh

  4. Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway

    Jorunn Pauline Cavanagh

  5. Clinical Microbiology and ATB Centre, Institute of Medical Biochemistry and Laboratory Diagnostics, General University Hospital, Prague, Czech Republic

    Jan Závora & Václava Adámková

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  1. Vladimir Vimberg
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Correspondence to Vladimir Vimberg.

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Vimberg, V., Gazak, R., Szűcs, Z. et al. Fluorescence assay to predict activity of the glycopeptide antibiotics. J Antibiot 72, 114–117 (2019). https://doi.org/10.1038/s41429-018-0120-5

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