2025
Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease
Yang Y, Duan Y, Lang S, Fondevila M, Schöler D, Harberts A, Cabré N, Chen S, Shao Y, Vervier K, Miyamoto Y, Zhang X, Chu H, Yang L, Tan C, Eckmann L, Bosques-Padilla F, Verna E, Abraldes J, Brown R, Vargas V, Altamirano J, Caballería J, Shawcross D, Louvet A, Lucey M, Mathurin P, Garcia-Tsao G, Bataller R, Stärkel P, Lawley T, Schnabl B. Targeted inhibition of pathobiont virulence factor mitigates alcohol-associated liver disease. Cell Host & Microbe 2025, 33: 957-972.e6. PMID: 40441146, PMCID: PMC12162233, DOI: 10.1016/j.chom.2025.05.003.Peer-Reviewed Original ResearchConceptsEthanol-induced liver diseaseAlcohol-associated liver diseaseAlcohol-associated hepatitisLiver diseaseGenome of Escherichia coliE. coliMetagenomic sequencing of fecal samplesInternational cohort of patientsGenetic manipulation of bacteriaGnotobiotic mouse modelOutcomes of patientsManipulation of bacteriaCohort of patientsScavenger receptor MARCOGlobal health burdenVirulence factorsMetagenomic sequencingGut microbiotaGenetic manipulationDisease progressionMouse modelKupffer cellsKpsMBacterial spreadInternational cohortNongenetic adaptation by collective migration
Vo L, Avgidis F, Mattingly H, Edmonds K, Burger I, Balasubramanian R, Shimizu T, Kazmierczak B, Emonet T. Nongenetic adaptation by collective migration. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2423774122. PMID: 39970001, PMCID: PMC11874451, DOI: 10.1073/pnas.2423774122.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalChemotaxisEscherichia coliEscherichia coli ProteinsGene Expression Regulation, BacterialPhenotypeConceptsGene regulationCollective migrationPhenotype distributionPhenotypic compositionStress response pathwaysSwimming phenotypeCell populationsBacterial populationsStress responseAbundance distributionMultidimensional phenotypesGenetic mutationsPhenotypeDiverse environmentsEnvironmental conditionsGenesMutationsSwimming behaviorChanging environmentDoubling timeMigrating populationCellsRegulationMigrationAdaptationEngineering a genomically recoded organism with one stop codon
Grome M, Nguyen M, Moonan D, Mohler K, Gurara K, Wang S, Hemez C, Stenton B, Cao Y, Radford F, Kornaj M, Patel J, Prome M, Rogulina S, Sozanski D, Tordoff J, Rinehart J, Isaacs F. Engineering a genomically recoded organism with one stop codon. Nature 2025, 639: 512-521. PMID: 39910296, PMCID: PMC11903333, DOI: 10.1038/s41586-024-08501-x.Peer-Reviewed Original ResearchMeSH KeywordsCodon, TerminatorEscherichia coliEscherichia coli ProteinsGenetic CodeGenetic EngineeringGenome, BacterialPeptide Termination FactorsProtein Biosynthesis
2024
RluA is the major mRNA pseudouridine synthase in Escherichia coli
Schaening-Burgos C, LeBlanc H, Fagre C, Li G, Gilbert W. RluA is the major mRNA pseudouridine synthase in Escherichia coli. PLOS Genetics 2024, 20: e1011100. PMID: 39241085, PMCID: PMC11421799, DOI: 10.1371/journal.pgen.1011100.Peer-Reviewed Original ResearchConceptsPseudouridine synthasesHigh-confidence sitesMRNA-modifying enzymesE. coli mRNAsStructure probing dataIdentified target sitesTarget siteDiverse eukaryotesBacterial mRNAsRNA modificationsRluAEscherichia coliSecondary structureE. coliTRNAPseudouridineRRNAStructural motifsMRNAModification capacityRecognition elementsSynthaseRNASequenceEukaryotesEnterococcus faecalis-derived adenine enhances enterohaemorrhagic Escherichia coli Type 3 Secretion System-dependent virulence
Martins F, Rosay T, Rajan A, Carter H, Turocy T, Mejia A, Crawford J, Maresso A, Sperandio V. Enterococcus faecalis-derived adenine enhances enterohaemorrhagic Escherichia coli Type 3 Secretion System-dependent virulence. Nature Microbiology 2024, 9: 2448-2461. PMID: 38965331, PMCID: PMC11585081, DOI: 10.1038/s41564-024-01747-1.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAnimalsCoculture TechniquesEnterococcus faecalisEnterocytesEnterohemorrhagic Escherichia coliEscherichia coli InfectionsEscherichia coli ProteinsGastrointestinal MicrobiomeGene Expression Regulation, BacterialHemolysin ProteinsHost-Pathogen InteractionsHumansHypoxanthineMiceType III Secretion SystemsVirulenceVirulence FactorsXanthineConceptsT3SS gene expressionType 3 secretion systemGene expressionAE lesion formationPromote colonization resistanceE. faecalisAdenine biosynthesisEHEC virulenceEffector translocationBacterial geneticsColonization resistanceEnteric pathogensT3SSLesion formationEHECSupplementation experimentsVirulencePathway activationAdenineEnhanced pathogenesisHost responseCo-infectionExpressionCo-cultureTranscriptomeDual function of LapB (YciM) in regulating Escherichia coli lipopolysaccharide synthesis
Shu S, Tsutsui Y, Nathawat R, Mi W. Dual function of LapB (YciM) in regulating Escherichia coli lipopolysaccharide synthesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2321510121. PMID: 38635633, PMCID: PMC11046580, DOI: 10.1073/pnas.2321510121.Peer-Reviewed Original ResearchMeSH KeywordsAmidohydrolasesEscherichia coliEscherichia coli ProteinsLipopolysaccharidesMembrane ProteinsMutationRubredoxinsConceptsLPS synthesisTetratricopeptide repeatCytoplasmic domainLevels of lipopolysaccharideCryo-EM structureGram-negative bacteriaLipopolysaccharide synthesisProtease FtsHRubredoxin domainLpxC activityTransmembrane helicesIn vivo analysisLpxCPseudomonas aeruginosaEnzymatic activityLapBFtsHAllosteric effectsYciMDual functionIn vitroTetratricopeptideAdaptorMotifDeacetylaseChaperone Hsp70 helps Salmonella survive infection-relevant stress by reducing protein synthesis
Chan C, Groisman E. Chaperone Hsp70 helps Salmonella survive infection-relevant stress by reducing protein synthesis. PLOS Biology 2024, 22: e3002560. PMID: 38574172, PMCID: PMC10994381, DOI: 10.1371/journal.pbio.3002560.Peer-Reviewed Original ResearchMeSH KeywordsBacteriaEscherichia coliEscherichia coli ProteinsHSP70 Heat-Shock ProteinsMagnesiumMolecular ChaperonesProtein FoldingSalmonellaConceptsRibosome associationProtein synthesisProtein homeostasisS. typhimuriumProtein folding capacityPreventing protein aggregationC-terminal amino acidsDomains of lifeProtein synthesis in vitroInhibit protein synthesisFolding capacityHsp70 chaperonesJ-domainSynthesis in vitroProtein foldingReduction of protein synthesisChaperone Hsp70DnaKRibosomeProtein aggregationChaperoneAmino acidsProteinStarvationHSP70
2023
Structure of the native chemotaxis core signaling unit from phage E-protein lysed E. coli cells
Cassidy C, Qin Z, Frosio T, Gosink K, Yang Z, Sansom M, Stansfeld P, Parkinson J, Zhang P. Structure of the native chemotaxis core signaling unit from phage E-protein lysed E. coli cells. MBio 2023, 14: e00793-23. PMID: 37772839, PMCID: PMC10653900, DOI: 10.1128/mbio.00793-23.Peer-Reviewed Original ResearchMeSH KeywordsBacterial ProteinsChemotaxisEscherichia coliEscherichia coli ProteinsMethyl-Accepting Chemotaxis ProteinsSignal TransductionConceptsCore signalling unitChemosensory arraysLyse E. coli cellsCryo-electron tomographyBacterial chemotaxisSignal transductionCell movementEscherichia coli</i>.Sensing machinerySensory signal transductionSignaling unitStructural basisMolecular mechanismsMechanistic hypothesesDesign new experimentsChemotaxisCellsComplete structurePhageMotilityTransductionMachineryUbiquitous behaviorFirst report of the mobile colistin resistance gene, mcr-1.26, in multidrug-resistant Escherichia coli isolated from retail chicken meat
Kassem I, Osman M, Hassan J, Sulaiman A, Mann D, Esseili M, Naas T, Deng X. First report of the mobile colistin resistance gene, mcr-1.26, in multidrug-resistant Escherichia coli isolated from retail chicken meat. Journal Of Global Antimicrobial Resistance 2023, 34: 176-178. PMID: 37429544, DOI: 10.1016/j.jgar.2023.07.005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Bacterial AgentsChickensColistinEscherichia coliEscherichia coli ProteinsHumansMeatConceptsMinimum inhibitory concentrationColistin resistanceColistin-resistant Escherichia coliKirby-Bauer disk diffusionMultidrug-resistant Escherichia coliMDR E. coliPlasmid replicon typesWhole-genome sequencingSequence typesColistin resistance geneRetail chicken meatBroth microdilution methodMobile colistin resistance geneReplicon typesSusceptibility testingIncX4 plasmidsFirst reportMultidrug resistanceWhole-genome sequencing analysisDepth phenotypicInhibitory concentrationDisk diffusionMicrodilution methodGenomic epidemiologyAntimicrobial resistance genes
2022
Structures of the CcmABCD heme release complex at multiple states
Li J, Zheng W, Gu M, Han L, Luo Y, Yu K, Sun M, Zong Y, Ma X, Liu B, Lowder EP, Mendez DL, Kranz RG, Zhang K, Zhu J. Structures of the CcmABCD heme release complex at multiple states. Nature Communications 2022, 13: 6422. PMID: 36307425, PMCID: PMC9616876, DOI: 10.1038/s41467-022-34136-5.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateBacterial Outer Membrane ProteinsBacterial ProteinsCytochromes cEscherichia coliEscherichia coli ProteinsHemeHemeproteinsConceptsHigh-resolution cryo-EM structuresResolution cryo-EM structureABC transporter complexAttachment of hemeCryo-EM structureLarge membrane complexesHeme-binding siteATP-binding siteATP-dependent releaseTransfer of hemeC-type cytochromesHeme chaperoneHeme traffickingCytochrome c proteinMembrane proteinsHeme transferTransporter complexMembrane complexATP hydrolysisStructural basisC proteinAMP-PNPFunctional studiesHeme releaseUnbound formDegradation of gene silencer is essential for expression of foreign genes and bacterial colonization of the mammalian gut
Choi J, Schmukler M, Groisman EA. Degradation of gene silencer is essential for expression of foreign genes and bacterial colonization of the mammalian gut. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2210239119. PMID: 36161931, PMCID: PMC9546599, DOI: 10.1073/pnas.2210239119.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsDNA-Binding ProteinsEscherichia coliEscherichia coli ProteinsGene Expression Regulation, BacterialGene SilencingMammalsMiceProtease LaConceptsH-NSForeign genesHeat-stable nucleoid-structuring (H-NS) proteinWild-type H-NSNucleoid-associated proteinsH-NS proteinsNucleoid structuring proteinHorizontal gene transferBacterial evolutionLon proteaseSilences expressionCorresponding genesForeign DNAMammalian gutMammalian hostsStructuring proteinGene silencersGenesMurine gutEnteric bacteriaGene transferBiofilm formationProteinGeneral mechanismColonizationRegulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli
Shu S, Mi W. Regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli. Nature Communications 2022, 13: 4576. PMID: 35931690, PMCID: PMC9356133, DOI: 10.1038/s41467-022-32277-1.Peer-Reviewed Original ResearchMeSH KeywordsAmidohydrolasesEscherichia coliEscherichia coli ProteinsGram-Negative BacteriaLipopolysaccharidesMembrane ProteinsConceptsRegulatory mechanismsAnti-adaptor proteinsFirst committed stepMost Gram-negative bacteriaEssential glycolipidEssential membraneGram-negative bacteriaTransmembrane helicesAdaptor proteinCommitted stepCytoplasmic domainFtsHLPS synthesisAnalysis unravelsLipopolysaccharide synthesisLapBEscherichia coliE. coliPermeability barrierProtein levelsLpxCProtease activityProteinColiYejMVaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney
Chaurasia R, Salovey A, Guo X, Desir G, Vinetz JM. Vaccination With Leptospira interrogans PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney. Frontiers In Cellular And Infection Microbiology 2022, 12: 926994. PMID: 35837473, PMCID: PMC9274288, DOI: 10.3389/fcimb.2022.926994.Peer-Reviewed Original ResearchConceptsLethal challenge infectionChallenge infectionBacterial loadC3H/HeJ miceKey target organClinical pathogenesisSevere leptospirosisOrgan infectionProtein immunizationHeJ miceSerovar CanicolaTarget organsAnimal modelsLeptospirosis pathogenesisCellular pathogenesisMicePathogenesisInfectionLeptospira interrogansVirulence factorsModifying proteinsImmunizationKidneyLeptospirosisLiverLetter to the Editor: First Report of the Detection of the Plasmid-Borne Colistin Resistance Gene, mcr-1.26, in Multidrug-Resistant Escherichia coli Isolated from a Domesticated Pigeon
Kassem I, Assi A, Osman M, Mann D, Li S, Deng X. Letter to the Editor: First Report of the Detection of the Plasmid-Borne Colistin Resistance Gene, mcr-1.26, in Multidrug-Resistant Escherichia coli Isolated from a Domesticated Pigeon. Microbial Drug Resistance 2022, 28: 821-823. PMID: 35639443, DOI: 10.1089/mdr.2021.0359.Peer-Reviewed Original Research
2021
Surface-tethered planar membranes containing the β-barrel assembly machinery: a platform for investigating bacterial outer membrane protein folding
Hall S, Clifton L, Sridhar P, Hardy D, Wotherspoon P, Wright J, Whitehouse J, Gamage N, Laxton C, Hatton C, Hughes G, Jeeves M, Knowles T. Surface-tethered planar membranes containing the β-barrel assembly machinery: a platform for investigating bacterial outer membrane protein folding. Biophysical Journal 2021, 120: 5295-5308. PMID: 34757080, PMCID: PMC8715194, DOI: 10.1016/j.bpj.2021.10.033.Peer-Reviewed Original ResearchMeSH KeywordsBacterial Outer Membrane ProteinsEscherichia coliEscherichia coli ProteinsProtein FoldingConceptsOuter membrane proteinsBAM complexOuter membraneInserts outer membrane proteinsOuter membrane protein functionsOuter membrane protein foldingOuter membrane of Gram-negative bacteriaMembrane of Gram-negative bacteriaMembrane protein foldingQuartz crystal microbalanceSelf-assembled monolayersGram-negative bacteriaPhospholipid bilayer environmentAssembly machineryProtein foldingCrystal microbalanceMembrane proteinsGold surfaceStructural characterizationBiological functionsPolarized neutron reflectometryDissipation monitoringBilayer environmentComplex foldingProteinSpread of ESC-, carbapenem- and colistin-resistant Escherichia coli clones and plasmids within and between food workers in Lebanon
Al-Mir H, Osman M, Drapeau A, Hamze M, Madec J, Haenni M. Spread of ESC-, carbapenem- and colistin-resistant Escherichia coli clones and plasmids within and between food workers in Lebanon. Journal Of Antimicrobial Chemotherapy 2021, 76: 3135-3143. PMID: 34534282, DOI: 10.1093/jac/dkab327.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnti-Bacterial AgentsCarbapenemsClone CellsColistinEscherichia coliEscherichia coli InfectionsEscherichia coli ProteinsHumansLebanonMicrobial Sensitivity TestsPlasmidsConceptsMDR E. coliCarriage rateColistin resistanceFood workersHigh carriage rateNon-duplicate isolatesMDR Escherichia coliMiddle-income countriesCarbapenem resistanceHealthy adultsE. coli lineagesDifferent STsPlasmid transmissionCarbapenemsClonal transmissionE. coliMonthly intervalsLebanese communityPlasmid spreadProbing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure–Activity Relationships and Facilitates Mechanism of Action Studies
Wernke KM, Tirla A, Xue M, Surovtseva YV, Menges FS, Herzon SB. Probing Microbiome Genotoxicity: A Stable Colibactin Provides Insight into Structure–Activity Relationships and Facilitates Mechanism of Action Studies. Journal Of The American Chemical Society 2021, 143: 15824-15833. PMID: 34524796, DOI: 10.1021/jacs.1c07559.Peer-Reviewed Original ResearchConceptsFanconi anemia DNA repair pathwayBiosynthetic gene clusterDNA repair pathwaysGene clusterRepair pathwaysDNA bindingBacterial phenotypesInduces DNAGenotoxic effectsHuman microbiomeColibactinBiosynthetic precursorNatural product structuresBiological studiesPathwayStructure-activity relationshipsAction studiesGenotoxic metabolitesOrganismsOncogenesisDNATumorigenesisMicrobiomeFacilitate mechanismsPhenotypeStudying bacterial chemosensory array with CryoEM
Qin Z, Zhang P. Studying bacterial chemosensory array with CryoEM. Biochemical Society Transactions 2021, 49: 2081-2089. PMID: 34495335, PMCID: PMC8589424, DOI: 10.1042/bst20210080.Peer-Reviewed Original ResearchConceptsChemosensory arraysBacterial chemosensory arrayThousands of proteinsGradients of nutrientsCell polesLipid nanodiscsChemosensory systemCryoEMBacterial minicellsStructural studiesBacteria cellsBacterial ghostsRecent advancesMinicellsStructural analysisNanodiscsProteinBacteriaNutrientsCellsVivoCryo-EM structures of Escherichia coli cytochrome bo3 reveal bound phospholipids and ubiquinone-8 in a dynamic substrate binding site
Li J, Han L, Vallese F, Ding Z, Choi SK, Hong S, Luo Y, Liu B, Chan CK, Tajkhorshid E, Zhu J, Clarke O, Zhang K, Gennis R. Cryo-EM structures of Escherichia coli cytochrome bo3 reveal bound phospholipids and ubiquinone-8 in a dynamic substrate binding site. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2106750118. PMID: 34417297, PMCID: PMC8403832, DOI: 10.1073/pnas.2106750118.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCryoelectron MicroscopyCytochrome b GroupEscherichia coliEscherichia coli ProteinsHemeOxidation-ReductionPhospholipidsProtein ConformationProton PumpsUbiquinoneConceptsHydrogen bondsMembrane scaffold protein (MSP) nanodiscsSide chainsMetal redox centerCryo-EM structureInternal water moleculesEscherichia coli cytochrome bo3Facilitate proton transferImidazole side chainIsoprene side chainAccess of waterCryogenic electron microscopyRedox centersWater moleculesProton transferSubunit IAqueous phaseConformation 1Respiratory cytochromesRelated cytochromesHydrophobic grooveUbiquinol oxidaseQuinol oxidaseCytochrome bo3Computational studyEscherichia coli-Derived γ‑Lactams and Structurally Related Metabolites Are Produced at the Intersection of Colibactin and Fatty Acid Biosynthesis
Kim CS, Turocy T, Moon G, Shine EE, Crawford JM. Escherichia coli-Derived γ‑Lactams and Structurally Related Metabolites Are Produced at the Intersection of Colibactin and Fatty Acid Biosynthesis. Organic Letters 2021, 23: 6895-6899. PMID: 34406772, PMCID: PMC10577019, DOI: 10.1021/acs.orglett.1c02461.Peer-Reviewed Original ResearchMeSH KeywordsDNA DamageEscherichia coliEscherichia coli ProteinsFatty AcidsHumansLactamsMolecular StructurePeptidesPolyketidesConceptsFatty acid biosynthesisAcid biosynthesisHybrid polyketide-nonribosomal peptideNuclear magnetic resonance spectroscopyΓ-lactam derivativesUnknown biological activityBiosynthetic logicMagnetic resonance spectroscopyCancer initiationColorectal cancer initiationStereochemical analysisΓ-lactamsColibactinResonance spectroscopyDiverse collectionBiosynthesisBiological activityAbundant metabolitesPathwayRelated metabolitesRelated structuresMetabolitesLociProteinSpectroscopy
This site is protected by hCaptcha and its Privacy Policy and Terms of Service apply