Characterization of the AmpC β-Lactamase from Burkholderia multivorans

Antimicrobial Agents and Chemotherapy
Scott A BeckaKrisztina M Papp-Wallace

Abstract

Burkholderia multivorans is a member of the Burkholderia cepacia 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 Bmultivorans, which possesses two β-lactamase genes, blapenA and blaAmpC PenA is a carbapenemase with a substrate profile similar to that of the Klebsiella pneumoniae carbapenemase (KPC); in addition, expression of PenA is inducible by β-lactams in Bmultivorans Here, we characterize AmpC from Bmultivorans ATCC 17616. AmpC possesses only 38 to 46% protein identity with non-Burkholderia AmpC proteins (e.g., PDC-1 and CMY-2). Among 49 clinical isolates of Bmultivorans, 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 toward β-lactams (i.e., nitrocefin and cephalothin). Moreover, avibactam was a poor inhibitor of AmpC1 (Kiapp > 600 μM), and acyl-enzyme complex formation with AmpC1 was slow, likely due to lack of productive interactions with active-site residues. Interestingly, immunoblotting using a poly...Continue Reading

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Citations

Dec 16, 2020·Antimicrobial Agents and Chemotherapy·Krisztina M Papp-WallaceAlita A Miller
Jan 5, 2021·ACS Infectious Diseases·Nichole K StewartSergei B Vakulenko
Jun 22, 2021·International Journal of Environmental Health Research·Jasna HrenovicBranka Bedenic
Aug 8, 2021·International Journal of Molecular Sciences·Fernando Sanz-GarcíaSara Hernando-Amado

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