2025
Bacterial and host enzymes modulate the pro-inflammatory response elicited by the peptidoglycan of Lyme disease agent Borrelia burgdorferi
McCausland J, Kloos Z, Irnov I, Sonnert N, Zhou J, Putnik R, Mueller E, Steere A, Palm N, Grimes C, Jacobs-Wagner C. Bacterial and host enzymes modulate the pro-inflammatory response elicited by the peptidoglycan of Lyme disease agent Borrelia burgdorferi. PLOS Pathogens 2025, 21: e1013324. PMID: 40623106, PMCID: PMC12279116, DOI: 10.1371/journal.ppat.1013324.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsBorrelia burgdorferiHost-Pathogen InteractionsHumansInflammationLyme DiseasePeptidoglycanConceptsImmune responsePost-antibiotic treatmentProinflammatory immune responseNOD2-dependent immune responsesPro-inflammatory responseHost sensingAntibiotic therapyPersistent arthritisImmune detectionImmune systemHuman cell linesCell linesSpirochete Borrelia burgdorferiB. burgdorferiLyme disease agent Borrelia burgdorferiPatientsIntermediate Signaling Mechanisms Regulating Human Fetal Membrane Responses to Gram‐Positive Bacterial Peptidoglycan
Georges H, Fischer A, Abrahams V. Intermediate Signaling Mechanisms Regulating Human Fetal Membrane Responses to Gram‐Positive Bacterial Peptidoglycan. American Journal Of Reproductive Immunology 2025, 93: e70090. PMID: 40435036, PMCID: PMC12124414, DOI: 10.1111/aji.70090.Peer-Reviewed Original ResearchConceptsToll-like receptorsPro-inflammatory cytokines IL-1bFetal membrane explantsHuman FM explantsPathogenesis of chorioamnionitisP65-NFkBResponse to Gram-positive bacteriaP38 MAPKElevated levelsTLR2 agonist peptidoglycanCytokines IL-1bChemokine IL-8FM explantsNeonatal morbidityPreterm birthStimulation of TLR4Fetal membranesMembrane weakeningIL-1BIL-8TLR7/8 activationMembrane explantsSecreted factorsERK signalingLipopolysaccharide stimulationThe peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness
McClune M, Ebohon O, Dressler J, Davis M, Tupik J, Lochhead R, Booth C, Steere A, Jutras B. The peptidoglycan of Borrelia burgdorferi can persist in discrete tissues and cause systemic responses consistent with chronic illness. Science Translational Medicine 2025, 17: eadr2955. PMID: 40267217, PMCID: PMC12207536, DOI: 10.1126/scitranslmed.adr2955.Peer-Reviewed Original ResearchConceptsAcute infectionPeripheral blood mononuclear cellsBlood mononuclear cellsMurine modelPostinfectious complicationsMononuclear cellsMinimal pathologyKupffer cellsPersistent symptomsLyme arthritisPublic health concernLiver occupationLiver accumulationInflamed jointsSecreted protein profileInfectionChronic illnessOrgan-specificPatientsSynovial fluidPathogenic molecules
2022
Exploitation of a Bacterium-Encoded Lytic Transglycosylase by a Human Oral Lytic Phage To Facilitate Infection
Cen L, Chang Y, Bedree JK, Ma Y, Zhong Q, Utter DR, Dong PT, Lux R, Bor B, Liu J, McLean JS, Le S, He X. Exploitation of a Bacterium-Encoded Lytic Transglycosylase by a Human Oral Lytic Phage To Facilitate Infection. Journal Of Virology 2022, 96: e01063-22. PMID: 36000841, PMCID: PMC9472602, DOI: 10.1128/jvi.01063-22.Peer-Reviewed Original ResearchConceptsLytic transglycosylaseLytic phagesPhage receptorsOral phageRemarkable host specificityHuman oral microbiomeSimilar expression levelsPeptidoglycan remodelingWhole-genome sequencingMutant backgroundBacterial physiologyHost specificityMicrobial communitiesSurface-grown cellsPhage populationsSensitive phenotypeBacterial hostsOral microbiomePeptidoglycan structureWild typeMetagenomic analysisMutantsSpontaneous mutantsXH001Frameshift mutationTranscriptome of Epibiont Saccharibacteria Nanosynbacter lyticus Strain TM7x During the Establishment of Symbiosis
Hendrickson EL, Bor B, Kerns KA, Lamont EI, Chang Y, Liu J, Cen L, Schulte F, Hardt M, Shi W, He X, McLean JS. Transcriptome of Epibiont Saccharibacteria Nanosynbacter lyticus Strain TM7x During the Establishment of Symbiosis. Journal Of Bacteriology 2022, 204: e00112-22. PMID: 35975994, PMCID: PMC9487520, DOI: 10.1128/jb.00112-22.Peer-Reviewed Original ResearchConceptsCandidate Phyla RadiationEstablishment of symbiosisStable symbiosisStress-related genesGene expressionReduced genomePeptidoglycan biosynthesisHost bacteriaHuman microbiomeBiosynthesis gene expressionMonophyletic radiationCell sizeEffector genesPartitioning genesObligate parasitesUnique organismsBiosynthetic pathwayHigher gene expressionCell shapeTransporter geneCell wallObligate epibiontsLow expressionSymbiosisCell cycleMycobacterial serine/threonine phosphatase PstP is phosphoregulated and localized to mediate control of cell wall metabolism
Shamma F, Rego E, Boutte C. Mycobacterial serine/threonine phosphatase PstP is phosphoregulated and localized to mediate control of cell wall metabolism. Molecular Microbiology 2022, 118: 47-60. PMID: 35670057, PMCID: PMC10070032, DOI: 10.1111/mmi.14951.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsCell WallMycobacterium tuberculosisPeptidoglycanPhosphoprotein PhosphatasesPhosphorylationSerineConceptsCell wall metabolismWall metabolismCell wall-related proteinsSerine/threonine proteinCell wall regulationPhosphomimetic mutationReversible phosphorylationThreonine phosphataseEnvironmental stressRegulatory proteinsCell wallCorresponding mutationMycobacterial cell wallAntibiotic toleranceNovel substrateFhaAProteinPstPMycobacterium smegmatisWag31Certain substratesPeptidoglycanPhosphorylationRegulationMajor mechanismCell 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 ResearchMeSH KeywordsAnimalsBacterial ProteinsCell WallMycobacterium smegmatisPenicillin-Binding ProteinsPeptidoglycanConceptsPenicillin 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 distribution
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 infectionAbscessusEnzymeCeftarolineImipenemThe peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the lyme disease spirochete
Davis MM, Brock AM, DeHart TG, Boribong BP, Lee K, McClune ME, Chang Y, Cramer N, Liu J, Jones CN, Jutras BL. The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the lyme disease spirochete. PLOS Pathogens 2021, 17: e1009546. PMID: 33984073, PMCID: PMC8118282, DOI: 10.1371/journal.ppat.1009546.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsBorrelia burgdorferiCell WallChemokines, CXCHumansLyme DiseasePeptidoglycanConceptsPeptidoglycan-associated proteinsCell envelopeUnbiased proteomic approachCryo-electron microscopyOxidative stress responseOuter membrane vesiclesGram-negative bacteriaDps homologueEnvelope integrityProteomic approachNapA mutantOuter membraneBacterial proteinsMutant bacteriaDNA bindingCritical residuesBiological functionsLyme disease spirocheteStress responseCellular DNAMembrane vesiclesPeptidoglycanEnvelope layersBacterial pathogensCellular studies
2020
Structure and reconstitution of a hydrolase complex that may release peptidoglycan from the membrane after polymerization
Schaefer K, Owens T, Page J, Santiago M, Kahne D, Walker S. Structure and reconstitution of a hydrolase complex that may release peptidoglycan from the membrane after polymerization. Nature Microbiology 2020, 6: 34-43. PMID: 33168989, PMCID: PMC7755832, DOI: 10.1038/s41564-020-00808-5.Peer-Reviewed Original ResearchConceptsMature peptidoglycanLipid IIMembrane proteinsPolytopic membrane proteinsPeptidoglycan cell wallCell wall assemblyCell wall hydrolasesCaaX proteasesGlycan strandsCell wall matrixNascent peptidoglycanMembrane-anchoredTransmembrane helicesPeptidoglycan strandsPeptidoglycanPeptidoglycan polymerCell wallProtein scaffoldHydrolaseWall assemblyWall matrixBacteriaActive siteProteinMembraneA 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 upregulationRodAMreBHFtsWHomologCellsPeptidoglycanAutolysinEstablishing rod shape from spherical, peptidoglycan-deficient bacterial spores
Zhang H, Mulholland GA, Seef S, Zhu S, Liu J, Mignot T, Nan B. Establishing rod shape from spherical, peptidoglycan-deficient bacterial spores. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 14444-14452. PMID: 32513721, PMCID: PMC7321990, DOI: 10.1073/pnas.2001384117.Peer-Reviewed Original ResearchConceptsBacterial actin homolog MreBFuture cell polesActin homolog MreBGTPase-activating proteinsMolecular motorsGram-negative bacteriumCell polesEukaryotic cellsSynthesis complexSpherical sporesWalled cellsRod shapeMglBMglAPG growthSporesMreBBacterial sporesGTPaseCellsCytoskeletonMyxococcusPeptidoglycanProteinBacteriumFluorescent 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 pathogensMechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase
Geiger T, Lara-Tejero M, Xiong Y, Galán JE. Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase. ELife 2020, 9: e53473. PMID: 31958059, PMCID: PMC6996933, DOI: 10.7554/elife.53473.Peer-Reviewed Original ResearchStaphylococcus aureus cell growth and division are regulated by an amidase that trims peptides from uncrosslinked peptidoglycan
Do T, Schaefer K, Santiago A, Coe K, Fernandes P, Kahne D, Pinho M, Walker S. Staphylococcus aureus cell growth and division are regulated by an amidase that trims peptides from uncrosslinked peptidoglycan. Nature Microbiology 2020, 5: 291-303. PMID: 31932712, PMCID: PMC7046134, DOI: 10.1038/s41564-019-0632-1.Peer-Reviewed Original ResearchConceptsPeptidoglycan synthesisCell divisionCell growthUncrosslinked peptidoglycanStem peptidesCell cycleDefects due to lossMembrane protein complexesTransposon screenPeptidoglycan synthasesDivision sitePartner proteinsAssembled enzymeSubcellular locationCell peripheryPolymerase activityProtein complexesDaughter cellsPeptidoglycanAssembly sitesStaphylococcus aureusAmidaseCell expansionSynthase activityPeptide
2019
Direction of Chain Growth and Substrate Preferences of Shape, Elongation, Division, and Sporulation-Family Peptidoglycan Glycosyltransferases
Welsh M, Schaefer K, Taguchi A, Kahne D, Walker S. Direction of Chain Growth and Substrate Preferences of Shape, Elongation, Division, and Sporulation-Family Peptidoglycan Glycosyltransferases. Journal Of The American Chemical Society 2019, 141: 12994-12997. PMID: 31386359, PMCID: PMC6738341, DOI: 10.1021/jacs.9b06358.Peer-Reviewed Original ResearchConceptsPeptidoglycan glycosyltransferasesSubstrate preferenceLipid IICell wallMature cell wallsBacterial cell wallGlycan strandsSEDS proteinsGlycan chainsDecades bacteriaPeptidoglycan polymerasesPeptidoglycanGlycopeptide precursorsLipid requirementsFtsWII monomerGlycosyltransferasesPolymeraseGlycansStructural studiesBacteriaRodAEnzymeLipidAntibiotics
2018
Maturing Mycobacterium smegmatis peptidoglycan requires non-canonical crosslinks to maintain shape
Baranowski C, Welsh M, Sham L, Eskandarian H, Lim H, Kieser K, Wagner J, McKinney J, Fantner G, Ioerger T, Walker S, Bernhardt T, Rubin E, Rego E. Maturing Mycobacterium smegmatis peptidoglycan requires non-canonical crosslinks to maintain shape. ELife 2018, 7: e37516. PMID: 30324906, PMCID: PMC6231781, DOI: 10.7554/elife.37516.Peer-Reviewed Original ResearchConceptsPenicillin-binding proteinsAsymmetric polar growthRod-shaped bacteriaPolar growthPolar elongationShape maintenanceCell wallGenetic relationshipsDrug targetsUnusual crosslinksD-transpeptidasesSingle cellsPeptidoglycanCellsCrosslinksProteinMycobacteriaBacteriaPathogensTypes of crosslinksElongationGrowthMaintenanceTargetPeptidoglycan editing by a specific ld-transpeptidase controls the muramidase-dependent secretion of typhoid toxin
Geiger T, Pazos M, Lara-Tejero M, Vollmer W, Galán JE. Peptidoglycan editing by a specific ld-transpeptidase controls the muramidase-dependent secretion of typhoid toxin. Nature Microbiology 2018, 3: 1243-1254. PMID: 30250245, PMCID: PMC7464686, DOI: 10.1038/s41564-018-0248-x.Peer-Reviewed Original ResearchConceptsProtein export mechanismProtein secretion mechanismsTyphoid toxinEssential virulence factorBacterial poleMammalian cellsPeptidoglycan layerMost bacterial pathogensOuter membraneExport mechanismSecretion mechanismToxin secretionBacterial speciesTranslocation processTrans sideVirulence factorsBacterial pathogensExtracellular spaceTransport pathwaysTarget cellsToxinTyphoid feverCellsSubsequent releaseSecretionAspartate 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 targetCellsCharacterization of Conserved and Novel Septal Factors in Mycobacterium smegmatis
Wu K, Zhang J, Baranowski C, Leung V, Rego E, Morita Y, Rubin E, Boutte C. Characterization of Conserved and Novel Septal Factors in Mycobacterium smegmatis. Journal Of Bacteriology 2018, 200: 10.1128/jb.00649-17. PMID: 29311277, PMCID: PMC5826036, DOI: 10.1128/jb.00649-17.Peer-Reviewed Original ResearchConceptsCell wallModel organismsCell wall regulationIntracellular membrane domainCell wall biosynthesisCell wall precursorsCell wall structureCritical regulatory functionsBacterial cell wallDifferent regulatory mechanismsWall biosynthesisDistant speciesMembrane domainsCoordinated regulationElongation functionStructural homologsWall precursorsDivision processRegulatory mechanismsHomologMycobacterial cell wallRegulatory functionsCell survivalDifferent regulatorsCell growth
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