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 ResearchDurlobactam, a Diazabicyclooctane β‑Lactamase Inhibitor, Inhibits BlaC and Peptidoglycan Transpeptidases of Mycobacterium tuberculosis
Nantongo M, Nguyen D, Bethel C, Taracila M, Li Q, Dousa K, Shin E, Kurz S, Nguyen L, Kreiswirth B, Boom W, Plummer M, Bonomo R. Durlobactam, a Diazabicyclooctane β‑Lactamase Inhibitor, Inhibits BlaC and Peptidoglycan Transpeptidases of Mycobacterium tuberculosis. ACS Infectious Diseases 2024, 10: 1767-1779. PMID: 38619138, DOI: 10.1021/acsinfecdis.4c00119.Peer-Reviewed Original ResearchConceptsESI-MSElectrospray ionization mass spectrometryIonization mass spectrometryB-lactamase inhibitorsAcyl-enzyme complexMycobacterial cell wall synthesisMolecular dockingMass spectrometryActive siteInhibit BlaCPeptidoglycan transpeptidaseDiazabicyclooctaneSynthesisAntibiotic susceptibility testingCell wall synthesisInhibition kineticsDrug targetsB-lactamaseDurlobactamSusceptibility testingComplexDockingSpectrometryWall synthesisPeptidoglycan synthesis
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
2021
1390. Durlobactam, a Diazabicyclooctane (DBO) β-lactamase Inhibitor (BLI), Inhibits BlaC and Peptidoglycan (PG) Transpeptidases of Mycobacterium tuberculosis (Mtb): A Novel Approach to Therapeutics for Tuberculosis (TB)?
Nguyen D, Bethel C, Taracilla M, Li Q, Dousa K, Kurz S, Nguyen L, Kreiswirth B, Boom W, Bonomo R. 1390. Durlobactam, a Diazabicyclooctane (DBO) β-lactamase Inhibitor (BLI), Inhibits BlaC and Peptidoglycan (PG) Transpeptidases of Mycobacterium tuberculosis (Mtb): A Novel Approach to Therapeutics for Tuberculosis (TB)? Open Forum Infectious Diseases 2021, 8: 780-780. PMCID: PMC8643912, DOI: 10.1093/ofid/ofab466.1582.Peer-Reviewed Original ResearchB-lactamMultidrug-resistant TBTreatment of TBNovel therapiesMtb H37RvAvibactamRelebactamCarbapenemsClavulanateMicrodilution methodAcyl-enzyme complexTherapeutic potentialDurlobactamMeropenemMICDual actionTranspeptidasePre-incubationDiazabicyclooctaneMtbAmoxicillinPeriod of pre-incubationTuberculosis
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 outcomes
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