Klebsiella pneumoniae Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering

The emergence of carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt...

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Veröffentlicht in:	mBio 2017-10, Vol.8 (5)
Hauptverfasser:	Barnes, Melissa D, Winkler, Marisa L, Taracila, Magdalena A, Page, Malcolm G, Desarbre, Eric, Kreiswirth, Barry N, Shields, Ryan K, Nguyen, Minh-Hong, Clancy, Cornelius, Spellberg, Brad, Papp-Wallace, Krisztina M, Bonomo, Robert A
Format:	Artikel
Sprache:	eng
Schlagworte:	Amino Acid Substitution Anti-Bacterial Agents - metabolism Anti-Bacterial Agents - pharmacology Asparagine - chemistry Asparagine - genetics Azabicyclo Compounds - metabolism Bacterial Proteins - chemistry Bacterial Proteins - genetics Bacterial Proteins - metabolism beta-Lactamases - chemistry beta-Lactamases - genetics beta-Lactamases - metabolism Ceftazidime - metabolism Drug Combinations Drug Resistance, Multiple, Bacterial - genetics Humans Kinetics Klebsiella Infections - microbiology Klebsiella pneumoniae - drug effects Klebsiella pneumoniae - enzymology Klebsiella pneumoniae - genetics Mass Spectrometry Microbial Sensitivity Tests Molecular Dynamics Simulation Mutation Phenotype Protein Engineering - methods
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