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
2024
Durlobactam, 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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