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Structural Mechanisms of β-Lactam Antibiotic Resistance in Penicillin-Binding Proteins

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Abstract

The effectiveness of β-lactam antibiotics is under siege by multiple pathogenic bacteria. These bacteria can produce β-lactamases that hydrolyze the antibiotic, alter their permeability by increasing efflux or decreasing influx (Gram-negative-specific), and structurally alter existing penicillin-binding proteins (PBPs) to lower the rate of acylation or obtain a completely new penicillin-binding protein with extremely low rates of acylation by most β-lactam antibiotics. This chapter focuses on the genetic, biochemical, and structural mechanisms involved in PBP-mediated resistance, with a particular emphasis on resistance mechanisms in the pathogenic Gram-negative pathogen, Neisseria gonorrhoeae.

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Authors and Affiliations

  1. Departments of Pharmacology and Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Robert A. Nicholas

  2. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, USA

    Christopher Davies

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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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Nicholas, R.A., Davies, C. (2012). Structural Mechanisms of β-Lactam Antibiotic Resistance in Penicillin-Binding Proteins. In: Dougherty, T., Pucci, M. (eds) Antibiotic Discovery and Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1400-1_11

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