Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against Mycobacterium abscessus
Dousa K, Shin E, Kurz S, Plummer M, Nantongo M, Bethel C, Taracila M, Nguyen D, Kreiswith B, Daley C, Remy K, Holland S, Bonomo R. Synergistic effects of sulopenem in combination with cefuroxime or durlobactam against Mycobacterium abscessus. MBio 2024, 15: e00609-24. PMID: 38742824, PMCID: PMC11237399, DOI: 10.1128/mbio.00609-24.Peer-Reviewed Original ResearchConceptsD,D-carboxypeptidaseMinimum inhibitory concentrationB-lactamPenicillin-binding-proteinCell wall synthesisL,D-transpeptidasesResistance to common antibioticsLowest minimum inhibitory concentrationWall synthesisCystic fibrosisD-carboxypeptidaseMass spectrometry analysisB-lactamaseThioester bondRate of treatment failureCell-based assaysMultiple antibioticsB-lactam ringsCommon antibioticsD-transpeptidasesB-lactamase inhibitorsCysteine residuesTime-kill studiesStructural lung diseaseMultidrug-resistant tuberculosisDurlobactam, 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
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