Characterization of the AmpC β-lactamase from <i>Burkholderia multivorans</i>.

Characterization of the AmpC β-lactamase from Burkholderia multivorans.

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Authors: Becka SA, Zeiser ET, Barnes MD, Taracila MA, Nguyen K, Singh I, Sutton GG, LiPuma JJ, Fouts DE, Papp-Wallace KM
Title: Characterization of the AmpC β-lactamase from Burkholderia multivorans.
Citation: Antimicrobial agents and chemotherapy. 2018-07-16; .: .
Abstract:
is a member of the complex, a group of >20 related species of nosocomial pathogens that commonly infect individuals suffering from Cystic Fibrosis. β-Lactam antibiotics are recommended as therapy for infections due to , which possesses two β-lactamase genes, and PenA is a carbapenemase with a substrate profile similar to the carbapenemase (KPC); in addition, expression of PenA is inducible by β-lactams in Herein, we characterize AmpC from ATCC 17616. AmpC possesses only 38-46% protein identity to non-Burkholderial AmpCs (e.g., PDC-1, CMY-2). Within 49 clinical isolates of , we identified 27 different AmpC variants. Some variants possessed single amino acid substitutions within critical active site motifs (Ω-loop and R2 loop). Purified AmpC1 demonstrated minimal measurable catalytic activity towards β-lactams (i.e., nitrocefin and cephalothin). Moreover, avibactam was a poor inhibitor of AmpC1 ( >600 μM) and the acyl-enzyme complex formation with AmpC1 was slow, likely due to lack of productive interactions with active site residues. Interestingly, immunoblotting using a polyclonal anti-AmpC antibody revealed that protein expression of AmpC1 was inducible in ATCC 17616 after growth in sub-inhibitory concentrations of imipenem (1 μg/ml). The AmpC is a unique inducible class C cephalosporinase that may play an ancillary role in compared to PenA, which is the dominant β-lactamase in ATCC 17616.
PMID: 30012762