2025
P-788. Exploring β-Lactam Interactions with DacB1: Unraveling Optimal Therapies for Combating Drug-Resistant Mycobacterium tuberculosis
Nantongo M, Nguyen D, Shin E, Bethel C, Taracila M, Dousa K, Kurz S, Nguyen L, Kreiswirth B, Boom W, Bonomo R. P-788. Exploring β-Lactam Interactions with DacB1: Unraveling Optimal Therapies for Combating Drug-Resistant Mycobacterium tuberculosis. Open Forum Infectious Diseases 2025, 12: ofae631.982. PMCID: PMC11778675, DOI: 10.1093/ofid/ofae631.982.Peer-Reviewed Original ResearchMinimum inhibitory concentrationAcyl-enzyme adductOxyanion holeB-lactamB-lactamasePeptidoglycan synthesis pathwayCarbonyl groupHydrophobic interactionsElectrospray ionization mass spectrometryAcyl-enzyme formationB-lactam antibioticsMichaelis-Menten complexC1‐methyl groupProtein motifsPeptidoglycan biosynthesisDrug-resistant Mycobacterium tuberculosisIonization mass spectrometryPeptidoglycan synthesisD-carboxypeptidaseAnalysis of meropenemB-lactamase inhibitorsClinical isolatesBroth microdilutionClinically achievable concentrationsSynthesis pathway
2020
1642. A Novel β-lactamase Inhibitor (Durlobactam, DUR) and β-Lactams Enhance Susceptibility Against Multidrug-Resistant (MDR) Mycobacterium abscessus (Mab)
Dousa K, Kurz S, Bethel C, Miller A, Bonomo R. 1642. A Novel β-lactamase Inhibitor (Durlobactam, DUR) and β-Lactams Enhance Susceptibility Against Multidrug-Resistant (MDR) Mycobacterium abscessus (Mab). Open Forum Infectious Diseases 2020, 7: s810-s811. PMCID: PMC7777676, DOI: 10.1093/ofid/ofaa439.1822.Peer-Reviewed Original ResearchMinimum inhibitory concentrationB-lactamAmbler class AB-lactamase inhibitorsStructural lung diseaseB-lactam antibioticsImprove treatment outcomesTargeting multiple stepsMiddlebrook 7H9 brothVisible bacterial growthB-lactamaseDurlobactamBlaMabClinical isolatesColony-forming unitsMechanism of actionLung infectionCell wall structureRestore susceptibilityClinical strainsHydrolyzed penicillinsNontuberculous mycobacteriaLung diseaseMAB isolatesTreatment outcomes1572. Combination Cefuroxime and Sulopenem is active in vitro against Mycobacterium abscessus
Dousa K, Nguyen D, Kurz S, Taracila M, Bethel C, Bonomo R. 1572. Combination Cefuroxime and Sulopenem is active in vitro against Mycobacterium abscessus. Open Forum Infectious Diseases 2020, 7: s785-s785. PMCID: PMC7778327, DOI: 10.1093/ofid/ofaa439.1752.Peer-Reviewed Original ResearchQualified Infectious Disease ProductFood and Drug AdministrationMab infectionClinical isolatesColony-forming unitsCell wall synthesis proteinsMycobacterium abscessusB-lactamOral step-down therapyNontuberculous mycobacteriaStep-down therapyUS Food and Drug AdministrationB-lactam antibioticsVisible bacterial growthMiddlebrook 7H9 brothCharacterized isolatesMIC distributionSynthesis proteinsClinical strainsOral formulationMAB isolatesClinical trialsActivity in vitroDrug AdministrationBacterial growthInsights into the l,d-Transpeptidases and d,d-Carboxypeptidase of Mycobacterium abscessus: Ceftaroline, Imipenem, and Novel Diazabicyclooctane Inhibitors
Dousa K, Kurz S, Taracila M, Bonfield T, Bethel C, Barnes M, Selvaraju S, Abdelhamed A, Kreiswirth B, Boom W, Kasperbauer S, Daley C, Bonomo R. Insights into the l,d-Transpeptidases and d,d-Carboxypeptidase of Mycobacterium abscessus: Ceftaroline, Imipenem, and Novel Diazabicyclooctane Inhibitors. Antimicrobial Agents And Chemotherapy 2020, 64: 10.1128/aac.00098-20. PMID: 32393499, PMCID: PMC7526840, DOI: 10.1128/aac.00098-20.Peer-Reviewed Original ResearchConceptsCeftaroline fosamilB-lactamB-lactamaseNontuberculous mycobacteriaB-lactamase inhibitorsD-carboxypeptidaseB-lactam antibioticsCell wall synthesis proteinsCeftarolineImipenemDiazabicyclooctane inhibitorSteady-state kinetic assaysAvibactamHighest acylation ratesMechanism-based approachGt;100-foldRelebactamSynthesis proteinsD-transpeptidasesKinetic assaysAcylation rateInhibitors
2018
786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection?
Dousa K, Kreiswirth B, Kurz S, Bonomo R. 786. Ceftaroline and Avibactam? Is This a Potential Combination for Mycobacterium abscessus Infection? Open Forum Infectious Diseases 2018, 5: s281-s281. PMCID: PMC6254396, DOI: 10.1093/ofid/ofy210.793.Peer-Reviewed Original ResearchB-lactamB-lactamase inhibitorsMycobacterium abscessus infectionB-lactam antibioticsBenefits of combinationB-lactamaseCeftarolineHydrolyzed penicillinsMycobacterium abscessusAvibactamDiazabicyclooctane inhibitorBlaMabMycobacterial infectionMicrodilution methodClinical modelDiazabicyclooctaneInhibitorsInfectionMICInhibited growthNovel combinationCarbapenemsPotential combinationRelebactamMIC90
2015
Kinetic and Structural Characterization of the Interaction of 6‑Methylidene Penem 2 with the β‑Lactamase from Mycobacterium tuberculosis
Hazra S, Kurz S, Wolff K, Nguyen L, Bonomo R, Blanchard J. Kinetic and Structural Characterization of the Interaction of 6‑Methylidene Penem 2 with the β‑Lactamase from Mycobacterium tuberculosis. Biochemistry 2015, 54: 5657-5664. PMID: 26237118, PMCID: PMC4795174, DOI: 10.1021/acs.biochem.5b00698.Peer-Reviewed Original ResearchConceptsB-lactamaseB-lactamPenem 2Inhibit BlaCActive site residuesB-lactam antibioticsMycobacterium tuberculosisCultures of M. tuberculosisRing openingSite residuesBoronic acidsConstitutive expressionSignificant growth inhibitionStructural characterizationMass spectrometryCompound formsCovalent complexM. tuberculosisGrowth inhibitionBinding inhibitorAcylated formEnzymeRingCompounds
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