Combinatorial active‐site variants confer sustained clavulanate resistance in BlaC β‐lactamase from Mycobacterium tuberculosis

  title={Combinatorial active‐site variants confer sustained clavulanate resistance in BlaC β‐lactamase from Mycobacterium tuberculosis},
  author={Philippe Egesborg and H{\'e}l{\`e}ne Carlettini and Jordan P Volpato and N. Doucet},
  journal={Protein Science},
  • Philippe Egesborg, Hélène Carlettini, +1 author N. Doucet
  • Published 2015
  • Biology, Medicine
  • Protein Science
  • Bacterial resistance to β‐lactam antibiotics is a global issue threatening the success of infectious disease treatments worldwide. Mycobacterium tuberculosis has been particularly resilient to β‐lactam treatment, primarily due to the chromosomally encoded BlaC β‐lactamase, a broad‐spectrum hydrolase that renders ineffective the vast majority of relevant β‐lactam compounds currently in use. Recent laboratory and clinical studies have nevertheless shown that specific β‐lactam–BlaC inhibitor… CONTINUE READING
    10 Citations

    Topics from this paper

    Hydrolysis of Clavulanate by Mycobacterium tuberculosis β-Lactamase BlaC Harboring a Canonical SDN Motif
    • 14
    • PDF
    Mechanistic investigation of resistance via drug-inactivating enzymes in Mycobacterium tuberculosis
    • 3
    Bis(benzoyl) phosphate inactivators of beta-lactamase C from Mtb.
    β-Lactam Resistance Mechanisms: Gram-Positive Bacteria and Mycobacterium tuberculosis.
    • 24
    • PDF
    Rôle du motif SDN dans l'inhibition et l'activité des β-lactamases des mycobactéries
    • Highly Influenced
    Protein engineering in the 21st century
    • R. Chica
    • Biology, Medicine
    • Protein science : a publication of the Protein Society
    • 2015
    • 10


    Can Inhibitor-Resistant Substitutions in the Mycobacterium tuberculosis β-Lactamase BlaC Lead to Clavulanate Resistance?: a Biochemical Rationale for the Use of β-Lactam–β-Lactamase Inhibitor Combinations
    • 27
    • Highly Influential
    • PDF
    Three Decades of β-Lactamase Inhibitors
    • 1,064
    • PDF
    Natural evolution of TEM-1 β-lactamase: experimental reconstruction and clinical relevance.
    • 182