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Glycopeptide Resistance

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Antibiotic Discovery and Development

Abstract

Glycopeptides such as vancomycin and teicoplanin are active against clinically important Gram-positive pathogens. They act by binding, in a noncovalent fashion, to the C-terminal D-alanine-D-alanine dipeptide of the peptidoglycan precursors, preventing their incorporation into the growing wall and thus inhibiting cell-wall formation. Emergence of vancomycin resistance in enterococci was reported in 1986, approximately 30 years after the introduction of this antibiotic into clinical practice. Since then, vancomycin resistant enterococci have spread worldwide and are now one of the most common types of bacteria implicated in nosocomial infections in numerous countries. Glycopeptide resistance is due to acquisition of operons that encode enzymes responsible for synthesis of modified peptidoglycan precursors and for elimination of the precursors normally synthesized by the host. The origin of the resistance genes remains unclear. The mobility of certain van gene clusters by conjugation and transposition is expected to facilitate transfer of glycopeptide resistance from Enterococcus to more pathogenic bacteria such as staphylococci and streptococci. This mobility was confirmed in 2002 when the first clinical methicillin-resistant Staphylococcus aureus, highly resistant to glycopeptides by acquisition of a van operon from Enterococcus, was reported in the USA.

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  1. Institut Pasteur, Unité des Agents Antibactériens, 25, rue du Docteur Roux, 75724, Cedex 15, Paris, France

    Bruno Périchon & Patrice Courvalin

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  1. Bruno Périchon
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  2. Patrice Courvalin
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Correspondence to Patrice Courvalin .

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  1. , Senior Principal Scientist, AstraZeneca Pharmaceuticals LP, Gatehouse Dr. 35, Waltham, 02451, Massachusetts, USA

    Thomas J. Dougherty

  2. Achillion Pharmaceuticals, Inc., George St. 300, New Haven, 06511, Connecticut, USA

    Michael J. Pucci

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Périchon, B., Courvalin, P. (2012). Glycopeptide Resistance. In: Dougherty, T., Pucci, M. (eds) Antibiotic Discovery and Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1400-1_15

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