2024
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
2022
An essential periplasmic protein coordinates lipid trafficking and is required for asymmetric polar growth in mycobacteria
Gupta K, Gwin C, Rahlwes K, Biegas K, Wang C, Park J, Liu J, Swarts B, Morita Y, Rego E. An essential periplasmic protein coordinates lipid trafficking and is required for asymmetric polar growth in mycobacteria. ELife 2022, 11: e80395. PMID: 36346214, PMCID: PMC9678360, DOI: 10.7554/elife.80395.Peer-Reviewed Original ResearchConceptsPeriplasmic proteinsPolar growthNew cell wall materialOld poleQuantitative time-lapse imagingAsymmetric polar growthCell wall synthesisCell envelope compositionCell wall materialTime-lapse imagingCellular asymmetryEssential proteinsBacterial geneticsEssential transporterSingle geneWall synthesisLipid traffickingPopulation of cellsPlasma membraneTMM transportUnknown functionBroad functionsMycolic acidsTrehalose monomycolateEnvelope compositionCell Wall Damage Reveals Spatial Flexibility in Peptidoglycan Synthesis and a Nonredundant Role for RodA in Mycobacteria
Melzer E, Kado T, García-Heredia A, Gupta K, Meniche X, Morita Y, Sassetti C, Rego E, Siegrist M. Cell Wall Damage Reveals Spatial Flexibility in Peptidoglycan Synthesis and a Nonredundant Role for RodA in Mycobacteria. Journal Of Bacteriology 2022, 204: e00540-21. PMID: 35543537, PMCID: PMC9210966, DOI: 10.1128/jb.00540-21.Peer-Reviewed Original ResearchConceptsPenicillin binding proteinsCell wall damagePeptidoglycan synthesisPeptidoglycan assemblyClass A Penicillin-Binding ProteinsNascent cell wallCell wall integrityCell wall assemblyCell-wall peptidoglycanCell wall synthesisRod-shaped bacteriaMycobacterium smegmatisPolar growthInternal turgorModel organismsMreB homologsNew inhibition strategyRod complexWall synthesisWall peptidoglycanWall integrityAnimal pathogensCell wallPathway functionSubcellular distributionInhibiting 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
2020
A regulatory pathway that selectively up-regulates elongasome function in the absence of class A PBPs
Patel Y, Zhao H, Helmann J. A regulatory pathway that selectively up-regulates elongasome function in the absence of class A PBPs. ELife 2020, 9: e57902. PMID: 32897856, PMCID: PMC7478892, DOI: 10.7554/elife.57902.Peer-Reviewed Original ResearchConceptsPenicillin-binding proteinsAlternative sigma factor σClass A Penicillin-Binding ProteinsSigma factor σSuppressor analysisMreB homologsPeptidoglycan assemblyCell elongationWall synthesisPeptidoglycan synthesisRegulatory pathwaysCell shapeTransglycosylase activityStress responseFunction mutationsFactor σAPBPsDependent upregulationRodAMreBHFtsWHomologCellsPeptidoglycanAutolysinFluorescent stem peptide mimics: In situ probes for peptidoglycan crosslinking
Gautam S, Kim T, Howell R, Spiegel DA. Fluorescent stem peptide mimics: In situ probes for peptidoglycan crosslinking. Methods In Enzymology 2020, 638: 57-67. PMID: 32416921, DOI: 10.1016/bs.mie.2020.02.016.Peer-Reviewed Case Reports and Technical NotesConceptsBacterial cell wall synthesisSynthetic probesPeptide mimicsPeptidoglycan crosslinkingSynthesisSitu probeKey stepCrosslinkingNumerous classesMechanical strengthNew antibioticsProbeCell wall synthesisPeptidoglycan synthesisSuper-resolution microscopyLive bacteriaWall synthesisReactionCell wallDetailed protocolMicroscopyStaphylococcus aureusHuman pathogens
2019
Mutations of the Bacillus subtilis YidC1 (SpoIIIJ) insertase alleviate stress associated with σM-dependent membrane protein overproduction
Zhao H, Sachla A, Helmann J. Mutations of the Bacillus subtilis YidC1 (SpoIIIJ) insertase alleviate stress associated with σM-dependent membrane protein overproduction. PLOS Genetics 2019, 15: e1008263. PMID: 31626625, PMCID: PMC6827917, DOI: 10.1371/journal.pgen.1008263.Peer-Reviewed Original ResearchConceptsCell wall synthesisWall synthesisHydrophilic grooveMembrane protein insertaseMembrane protein overproductionIntegral membrane proteinsDNA damage responseSingle amino acid substitutionAmino acid substitutionsProtein translocaseSecretion stressFitness defectsOxidative stressDamage responseMembrane proteinsProtein overproductionRegulon inductionCell wallRegulonAcid substitutionsB. subtilisBacillus subtilisFunction mutationsCell deathCell growthDeciphering the essentiality and function of the anti‐σM factors in Bacillus subtilis
Zhao H, Roistacher D, Helmann J. Deciphering the essentiality and function of the anti‐σM factors in Bacillus subtilis. Molecular Microbiology 2019, 112: 482-497. PMID: 30715747, PMCID: PMC6679829, DOI: 10.1111/mmi.14216.Peer-Reviewed Original ResearchConceptsAnti-sigma factorAlternative sigma factorSigma factorRNA polymerase core enzymeCell wall homeostasisStress conditionsSigma factor activitySevere growth defectBeta prime subunitCell wall synthesisAbility of mutationsDepletion strainCore enzymeTranscriptional landscapeSuppressor mutationsGrowth defectMerodiploid strainsRNA polymeraseWall synthesisMutations mapWall homeostasisAccessory proteinsPositive feedback loopBacillus subtilisFactor activity
2018
Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis
Zhao H, Roistacher D, Helmann J. Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis. Molecular Microbiology 2018, 109: 826-844. PMID: 29995990, PMCID: PMC6185803, DOI: 10.1111/mmi.14078.Peer-Reviewed Original ResearchConceptsDifco sporulation mediumPeptidoglycan synthesisCentral metabolismCell envelope stress responseEnvelope stress responseCell wall synthesisCell lysisWall synthesisSensitizes cellsStress responseAlteration of metabolismUptake systemBacillus subtilisLater stepsAmino acid analysisDiaminopimelateLB mediumSporulation mediumAcid analysisPhysiological studiesSynthesis inhibitorCompetitive inhibitorMetabolismImportant targetCells
2017
Don’t let sleeping dogmas lie: new views of peptidoglycan synthesis and its regulation
Zhao H, Patel V, Helmann J, Dörr T. Don’t let sleeping dogmas lie: new views of peptidoglycan synthesis and its regulation. Molecular Microbiology 2017, 106: 847-860. PMID: 28975672, PMCID: PMC5720918, DOI: 10.1111/mmi.13853.Peer-Reviewed Original ResearchConceptsCell wall biogenesisCell wall synthesisWall biogenesisWall synthesisBacterial cell wall biogenesisCell wall synthesis processRod-shaped bacteriaBacterial cell wall synthesisSingle-molecule trackingPeptidoglycan synthesisCell wallMolecule trackingIntense research focusBiogenesisBacteriaCircumstantial evidencePowerful antibioticsFundamental questionsRegulationTechnical limitationsBiochemistryNew dataTemporal mappingSynthesisOld observationsDeletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity
Rego E, Audette R, Rubin E. Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity. Nature 2017, 546: 153-157. PMID: 28569798, PMCID: PMC5567998, DOI: 10.1038/nature22361.Peer-Reviewed Original Research
2015
Chemical Probes Reveal an Extraseptal Mode of Cross-Linking in Staphylococcus aureus
Gautam S, Kim T, Spiegel DA. Chemical Probes Reveal an Extraseptal Mode of Cross-Linking in Staphylococcus aureus. Journal Of The American Chemical Society 2015, 137: 7441-7447. PMID: 26035224, DOI: 10.1021/jacs.5b02972.Peer-Reviewed Original ResearchConceptsCross-linking activityPenicillin-binding proteinsCell divisionPeptidoglycan synthesisCell wall biogenesisEnzyme cross-linking activityCell wall synthesisWall biogenesisModel organismsWall synthesisImportant human pathogenCell wallChemical probesEndogenous substratesHuman pathogensSpherical bacteriaPBP4Distinct modesPeripheral wallDivisionBiogenesisS. aureusOrganismsStaphylococcus aureusProtein
2014
Accumulation of heptaprenyl diphosphate sensitizes Bacillus subtilis to bacitracin: implications for the mechanism of resistance mediated by the BceAB transporter
Kingston A, Zhao H, Cook G, Helmann J. Accumulation of heptaprenyl diphosphate sensitizes Bacillus subtilis to bacitracin: implications for the mechanism of resistance mediated by the BceAB transporter. Molecular Microbiology 2014, 93: 37-49. PMID: 24806199, PMCID: PMC4077933, DOI: 10.1111/mmi.12637.Peer-Reviewed Original Research
2013
The mechanics of shape in prokaryotes.
Wang S, Shaevitz JW. The mechanics of shape in prokaryotes. Frontiers In Bioscience-Scholar 2013, 5: 564-74. PMID: 23277069, DOI: 10.2741/s390.Peer-Reviewed Original ResearchConceptsCell wallBacterial cell morphogenesisCell shape maintenanceCell wall growthCell wall synthesisOverall cell shapeBacterial cell wallBacterial cytoskeletonCell morphogenesisWall synthesisShape maintenanceCell shapeWall growthSelective benefitsCellular scaleCytoskeletonRecent studiesProkaryotesTransglycosylasesMorphogenesisPeptidoglycanTranspeptidasesGrowthBacteriaDigests
2012
Helical insertion of peptidoglycan produces chiral ordering of the bacterial cell wall
Wang S, Furchtgott L, Huang KC, Shaevitz JW. Helical insertion of peptidoglycan produces chiral ordering of the bacterial cell wall. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: e595-e604. PMID: 22343529, PMCID: PMC3309786, DOI: 10.1073/pnas.1117132109.Peer-Reviewed Original ResearchConceptsHelical insertionCell wallGlycan strandsCell shapeRod-shaped bacterium Escherichia coliPeptidoglycan cell wallCell wall architectureCell growthRod-shaped bacteriaBacillus subtilis cellsBacterium Escherichia coliCell wall networkBacterial cell wallMreB cytoskeletonNanometer-sized proteinsBacterial cytoskeletonBiological kingdomsWall synthesisPeptidoglycan networkSubtilis cellsTurgor pressureEscherichia coliElongational growthCytoskeletonCommon mechanism
2008
Prioritization of gene regulatory interactions from large-scale modules in yeast
Lee HJ, Manke T, Bringas R, Vingron M. Prioritization of gene regulatory interactions from large-scale modules in yeast. BMC Bioinformatics 2008, 9: 32. PMID: 18211684, PMCID: PMC2244593, DOI: 10.1186/1471-2105-9-32.Peer-Reviewed Original ResearchConceptsTranscriptional modulesRegulatory interactionsTarget genesTranscription factorsChIP-chip binding dataTF-gene interactionsGene regulatory interactionsCo-regulated proteinsCo-regulated genesNormal growth conditionsGenome-wide dataCell wall synthesisChIP-chip dataRegulatory linkWall synthesisFunctional categoriesRegulatory proteinsYeast dataGenesCoherent modulesGrowth conditionsProteinBiological systemsDifferent reference datasetsNumerous modules
2007
Distribution of Protein A on the Surface of Staphylococcus aureus
DeDent AC, McAdow M, Schneewind O. Distribution of Protein A on the Surface of Staphylococcus aureus. Journal Of Bacteriology 2007, 189: 4473-4484. PMID: 17416657, PMCID: PMC1913371, DOI: 10.1128/jb.00227-07.Peer-Reviewed Original Research
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