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
1432. Exploring Cell Wall Targets to Overcome Mycobacterium tuberculosis (Mtb): Ceftriaxone (CRO) Inhibits LdtMt2, a Major Peptidoglycan (PG) Synthase
Nguyen D, Redmond S, Dousa K, Bethel C, Taracila M, Li Q, Kurz S, Pavelka M, Papp-Wallace K, Holland S, Kreiswirth B, Boom H, Bonomo R. 1432. Exploring Cell Wall Targets to Overcome Mycobacterium tuberculosis (Mtb): Ceftriaxone (CRO) Inhibits LdtMt2, a Major Peptidoglycan (PG) Synthase. Open Forum Infectious Diseases 2022, 9: ofac492.1261. PMCID: PMC9752925, DOI: 10.1093/ofid/ofac492.1261.Peer-Reviewed Original ResearchDrug-resistant tuberculosisB-lactamaseMTB isolatesDifficult-to-treat infectionsB-lactamase inhibitorsFractional inhibitory concentration indexMultidrug-resistant mycobacteriaIn vitro susceptibilityCystic Fibrosis FoundationBroth microdilution methodPG synthasesElectrospray ionization-mass spectrometryCeftriaxone MICsDR-TBSusceptibility testingImipenemMeropenemTB guidelinesCeftriaxoneB-lactamTreatment strategiesClinical studiesLowered MICClavulanateMicrodilution methodInhibiting 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
“One-Two Punch”: Synergistic ß-Lactam Combinations for Mycobacterium abscessus and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes
Nguyen D, Dousa K, Kurz S, Brown S, Drusano G, Holland S, Kreiswirth B, Boom W, Daley C, Bonomo R. “One-Two Punch”: Synergistic ß-Lactam Combinations for Mycobacterium abscessus and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes. Clinical Infectious Diseases 2021, 73: 1532-1536. PMID: 34113990, PMCID: PMC8677594, DOI: 10.1093/cid/ciab535.Peer-Reviewed Original ResearchConceptsPeptidoglycan synthesis enzymesMinimum inhibitory concentration of clinical isolatesB-lactamCombination of imipenemSynthesis enzymesSynergistic in vitroClinical isolatesMinimum inhibitory concentrationMycobacterium abscessusClinical trialsMycobacterial infectionAbscessusEnzymeCeftarolineImipenem
2020
Insights 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
2019
1385. Mechanism-Based, In Vitro Inhibition of Mycobacterium abscessus: Assessing β-Lactam Therapy
Dousa K, Kurz S, Bethel C, Barnes M, Taracilla M, Selvaraju S, Jacobs M, Kreiswirth B, Kasperbauer S, Daley C, Bonomo R. 1385. Mechanism-Based, In Vitro Inhibition of Mycobacterium abscessus: Assessing β-Lactam Therapy. Open Forum Infectious Diseases 2019, 6: s503-s503. PMCID: PMC6809419, DOI: 10.1093/ofid/ofz360.1249.Peer-Reviewed Original ResearchB-lactamaseColony-forming unitsIn vitro susceptibility testingB-lactamase inhibitorsTherapeutically achievable concentrationsMab infectionRescue regimenMiddlebrook 7H9 brothVisible bacterial growthSusceptibility testingClinical isolatesImipenemBlaMabTreated patientsRelebactamAvibactamNontuberculous mycobacteriaB-lactamM. abscessusMAB isolatesTest agentsIn vitro inhibitionMAb complexesMAbMIC
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