2024
Durlobactam in combination with β-lactams to combat Mycobacterium abscessus
Shin E, Dousa K, Taracila M, Bethel C, Nantongo M, Nguyen D, Akusobi C, Kurz S, Plummer M, Daley C, Holland S, Rubin E, Bulitta J, Boom W, Kreiswirth B, Bonomo R. Durlobactam in combination with β-lactams to combat Mycobacterium abscessus. Antimicrobial Agents And Chemotherapy 2024, 69: e01174-24. PMID: 39714147, PMCID: PMC11823594, DOI: 10.1128/aac.01174-24.Peer-Reviewed Original Research
2022
Inhibiting Mycobacterium abscessus Cell Wall Synthesis: Using a Novel Diazabicyclooctane β-Lactamase Inhibitor To Augment β-Lactam Action
Dousa K, Nguyen D, Kurz S, Taracila M, Bethel C, Schinabeck W, Kreiswirth B, Brown S, Boom W, Hotchkiss R, Remy K, Jacono F, Daley C, Holland S, Miller A, Bonomo R. Inhibiting Mycobacterium abscessus Cell Wall Synthesis: Using a Novel Diazabicyclooctane β-Lactamase Inhibitor To Augment β-Lactam Action. MBio 2022, 13: e03529-21. PMID: 35073757, PMCID: PMC8787486, DOI: 10.1128/mbio.03529-21.Peer-Reviewed Original ResearchConceptsD-carboxypeptidaseB-lactamB-lactamaseDisrupt cell wall synthesisStable acyl-enzyme complexesCell wall synthesisAcyl-enzyme complexMichaelis-Menten complexB-lactamase inhibitorsWall synthesisPeptidoglycan synthesisStructural lung diseaseTriple drug combinationIsolates to amoxicillinCell-based assaysMycobacterium abscessusMIC rangeImipenemMichaelis constantAcylation rateInhibitor combinationsDurlobactamMultidrug resistanceTherapeutic regimensCystic fibrosis
2013
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
Kurz S, Wolff K, Hazra S, Bethel C, Hujer A, Smith K, Xu Y, Tremblay L, Blanchard J, Nguyen L, Bonomo R. 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. Antimicrobial Agents And Chemotherapy 2013, 57: 6085-6096. PMID: 24060876, PMCID: PMC3837893, DOI: 10.1128/aac.01253-13.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SubstitutionAntitubercular Agentsbeta-Lactamase Inhibitorsbeta-LactamasesClavulanic AcidDrug Therapy, CombinationEscherichia coliExtensively Drug-Resistant TuberculosisGene ExpressionHumansMeropenemMicrobial Sensitivity TestsMutagenesis, Site-DirectedMycobacterium tuberculosisProtein EngineeringRecombinant ProteinsThienamycinsConceptsInhibitor combinationsResistance to clavulanic acidMultidrug resistanceDrug resistanceClavulanic acidExtensively drug-resistant M. tuberculosis strainsEmergence of multidrug resistanceCombination of meropenemDrug-resistant M. tuberculosis strainsPresence of ampicillinAmino acid residuesExtensively drug-resistantM. tuberculosis strainsNovel treatment strategiesInhibition of growthPotential therapeutic targetTreatment regimensTherapeutic modalitiesTreatment strategiesInhibitor resistanceM. tuberculosisEnzymatic assayImpaired inhibitionTherapeutic targetAcid resistance
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