2024
Bacterial Organelles in Iron Physiology
Ferrara K, Gupta K, Pi H. Bacterial Organelles in Iron Physiology. Molecular Microbiology 2024, 122: 914-928. PMID: 39545931, PMCID: PMC11659020, DOI: 10.1111/mmi.15330.Peer-Reviewed Original ResearchMembrane-bound organellesBacterial organellesFerritin-like proteinsEukaryotic organellesProtein-lipid monolayersEukaryotic cellsProteinaceous shellSpecies-specificBacterial cellsOrganellesProtecting cellsLife formsBiochemical reactionsPhysiological functionsDiverse arrayIron physiologyEnvironmental conditionsLipid bilayerBacteriaEssential micronutrientCellsSpecial structureBiogenesisGeneticsProtein
2023
Clostridioides difficile ferrosome organelles combat nutritional immunity
Pi H, Sun R, McBride J, Kruse A, Gibson-Corley K, Krystofiak E, Nicholson M, Spraggins J, Zhou Q, Skaar E. Clostridioides difficile ferrosome organelles combat nutritional immunity. Nature 2023, 623: 1009-1016. PMID: 37968387, PMCID: PMC10822667, DOI: 10.1038/s41586-023-06719-9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacterial ProteinsCell MembraneClostridioides difficileClostridium InfectionsCryoelectron MicroscopyDisease Models, AnimalElectron Microscope TomographyFerric CompoundsHomeostasisHost Microbial InteractionsInflammationIntestinesIronLeukocyte L1 Antigen ComplexMiceMicrobial ViabilityOrganellesConceptsFerric uptake regulator FurCryo-electron tomographyRegulator FurGram-negative bacteriaMembrane proteinsNutritional immunityIron uptakeCellular membranesDetoxification strategiesIron homeostasisForms of lifeStore ironBacterial pathogensIron sequestrationBiomineralization processPhosphate biomineralsRecent studiesImportant roleBacterial colonizationOrganellesInflamed gutMouse modelProteinTransportersHomeostasis
2022
Bacterial hydrophilins promote pathogen desiccation tolerance
Green E, Fakhoury J, Monteith A, Pi H, Giedroc D, Skaar E. Bacterial hydrophilins promote pathogen desiccation tolerance. Cell Host & Microbe 2022, 30: 975-987.e7. PMID: 35413266, PMCID: PMC9283220, DOI: 10.1016/j.chom.2022.03.019.Peer-Reviewed Original ResearchAn RNA-binding protein acts as a major post-transcriptional modulator in Bacillus anthracis
Pi H, Weiss A, Laut C, Grunenwald C, Lin H, Yi X, Stauff D, Skaar E. An RNA-binding protein acts as a major post-transcriptional modulator in Bacillus anthracis. Nature Communications 2022, 13: 1491. PMID: 35314695, PMCID: PMC8938561, DOI: 10.1038/s41467-022-29209-4.Peer-Reviewed Original ResearchConceptsHuman pathogen Bacillus anthracisRNA-binding proteinPost-transcriptional modulatorsPathogen Bacillus anthracisDetectable nuclease activityTwo-component systemBacillus anthracisGenetic competenceRNA turnoverDNA repairMRNA stabilityCellular metabolismNuclease activityEnvelope damageRNAProteinMultiple processesAnthracisHITRSporulationGenesMRNAExpressionMetabolismTurnoverA Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress
Wendel B, Pi H, Krüger L, Herzberg C, Stülke J, Helmann J. A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress. MBio 2022, 13: e00092-22. PMID: 35164567, PMCID: PMC8844918, DOI: 10.1128/mbio.00092-22.Peer-Reviewed Original ResearchConceptsResumption of growthOsmotic stressCompatible solutesCellular responsesBacillus subtilisDomains of lifeHigh salt stressCommon cellular responseEssential second messengerSpecific efflux pumpsSalt stressProtein translationOsmotic upshiftHyperosmotic stressSecond messengerHigh osmolarityReimportLiving cellsTransient growth inhibitionEfflux pumpsModel system
2021
DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis
Laut C, Leasure C, Pi H, Carlin S, Chu M, Hillebrand G, Lin H, Yi X, Stauff D, Skaar E. DnaJ and ClpX Are Required for HitRS and HssRS Two-Component System Signaling in Bacillus anthracis. Infection And Immunity 2021, 90: e00560-21. PMID: 34748369, PMCID: PMC8788696, DOI: 10.1128/iai.00560-21.Peer-Reviewed Original ResearchConceptsTwo-component systemGene expressionSubstrate-binding subunitSignal transduction activityTarget gene expressionB. anthracisBacillus anthracisGram-positive bacteriumHost-induced stressesClpXP proteaseProtein chaperonesSignal transductionClpXGene productsTransduction activityDnaJVertebrate hostsHeme levelsHomeostasis regulatorGenetic selectionHigh heme levelsCell envelope disruptionBioterror weaponHssRSAnthracis
2020
Directed evolution reveals the mechanism of HitRS signaling transduction in Bacillus anthracis
Pi H, Chu M, Ivan S, Latario C, Toth A, Carlin S, Hillebrand G, Lin H, Reppart J, Stauff D, Skaar E. Directed evolution reveals the mechanism of HitRS signaling transduction in Bacillus anthracis. PLOS Pathogens 2020, 16: e1009148. PMID: 33362282, PMCID: PMC7790381, DOI: 10.1371/journal.ppat.1009148.Peer-Reviewed Original ResearchConceptsHAMP domainSignal transductionGenetic selectionUnbiased genetic selectionCell envelope stressPathogen Bacillus anthracisSignal transduction systemImportant signal transduction systemMechanistic understandingBacillus anthracisComprehensive mechanistic understandingNumerous point mutationsEnvelope stressTransduction systemMolecular basisMutational analysisPoint mutationsTransductionRate-limiting stepIndividual domainsSpecific interactionsSignal sensingHITRAnthracisSystematic characterizationDysregulation of Magnesium Transport Protects Bacillus subtilis against Manganese and Cobalt Intoxication
Pi H, Wendel B, Helmann J. Dysregulation of Magnesium Transport Protects Bacillus subtilis against Manganese and Cobalt Intoxication. Journal Of Bacteriology 2020, 202: 10.1128/jb.00711-19. PMID: 31964700, PMCID: PMC7167470, DOI: 10.1128/jb.00711-19.Peer-Reviewed Original Research
2018
Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in Bacillus subtilis
Pi H, Helmann J. Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in Bacillus subtilis. MBio 2018, 9: 10.1128/mbio.01451-18. PMID: 30377275, PMCID: PMC6212828, DOI: 10.1128/mbio.01451-18.Peer-Reviewed Original ResearchConceptsRegulatory networksCatechol degradationPutative DNA binding sitesGenome-wide identificationGenome-wide characterizationFerric uptake regulatorIron-dependent transcriptional repressorCellular iron requirementsDNA binding sitesIron-sufficient conditionsIron-limiting conditionsHigh-affinity iron chelatorsEnvironmental aromatic compoundsSiderophore bacillibactinFur regulonGenomic viewApo-FurRepressor functionTranscriptional repressorRegulated genesChromatin immunoprecipitationPositive regulatorIron acquisitionNegative regulationGenetic analysisAntagonism of Two Plant-Growth Promoting Bacillus velezensis Isolates Against Ralstonia solanacearum and Fusarium oxysporum
Cao Y, Pi H, Chandrangsu P, Li Y, Wang Y, Zhou H, Xiong H, Helmann J, Cai Y. Antagonism of Two Plant-Growth Promoting Bacillus velezensis Isolates Against Ralstonia solanacearum and Fusarium oxysporum. Scientific Reports 2018, 8: 4360. PMID: 29531357, PMCID: PMC5847583, DOI: 10.1038/s41598-018-22782-z.Peer-Reviewed Original ResearchConceptsPlant growthRalstonia solanacearumBacillus velezensisFusarium oxysporumPathogen F. oxysporumStrong antagonistic activityRhizosphere colonizationSpore-forming bacilliBiocontrol agentsR. solanacearumB. velezensisCell motilityBiological processesF. oxysporumGreenhouse conditionsSolanacearumBiofilm formationOxysporumLP productionAntagonistic activityLipopeptide compoundsIturinRhizobacteriaPrimary rolePGPR
2017
Sequential induction of Fur-regulated genes in response to iron limitation in Bacillus subtilis
Pi H, Helmann J. Sequential induction of Fur-regulated genes in response to iron limitation in Bacillus subtilis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 12785-12790. PMID: 29133393, PMCID: PMC5715773, DOI: 10.1073/pnas.1713008114.Peer-Reviewed Original ResearchConceptsFerric uptake regulatorHigh-affinity FeIron availabilityPerR regulonFur regulonSiderophore bacillibactinGenetic toolsChIP experimentsIron limitationCell transitionBacillus subtilisHigh-affinity bindingIron homeostasisBacterial cellsIntracellular ironSequential inductionRegulonBacillibactinEnzyme accessVivo occupancyGenesFurIron poolIron sufficiencyEfflux transportersFerrous iron efflux systems in bacteria
Pi H, Helmann J. Ferrous iron efflux systems in bacteria. Metallomics 2017, 9: 840-851. PMID: 28604884, PMCID: PMC5675029, DOI: 10.1039/c7mt00112f.Peer-Reviewed Original Research
2016
The Listeria monocytogenes Fur‐regulated virulence protein FrvA is an Fe(II) efflux P1B4‐type ATPase
Pi H, Patel S, Argüello J, Helmann J. The Listeria monocytogenes Fur‐regulated virulence protein FrvA is an Fe(II) efflux P1B4‐type ATPase. Molecular Microbiology 2016, 100: 1066-1079. PMID: 26946370, PMCID: PMC4914386, DOI: 10.1111/mmi.13368.Peer-Reviewed Original Research
2015
Discovery of Antibiotic (E)‑3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)‑one
Bouley R, Kumarasiri M, Peng Z, Otero L, Song W, Suckow M, Schroeder V, Wolter W, Lastochkin E, Antunes N, Pi H, Vakulenko S, Hermoso J, Chang M, Mobashery S. Discovery of Antibiotic (E)‑3-(3-Carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)‑one. Journal Of The American Chemical Society 2015, 137: 1738-1741. PMID: 25629446, PMCID: PMC4607046, DOI: 10.1021/jacs.5b00056.Peer-Reviewed Original ResearchStructure–Activity Relationship for the Oxadiazole Class of Antibiotics
Spink E, Ding D, Peng Z, Boudreau M, Leemans E, Lastochkin E, Song W, Lichtenwalter K, O’Daniel P, Testero S, Pi H, Schroeder V, Wolter W, Antunes N, Suckow M, Vakulenko S, Chang M, Mobashery S. Structure–Activity Relationship for the Oxadiazole Class of Antibiotics. Journal Of Medicinal Chemistry 2015, 58: 1380-1389. PMID: 25590813, PMCID: PMC6863074, DOI: 10.1021/jm501661f.Peer-Reviewed Original ResearchConceptsMethicillin-resistant S. aureusStructure-activity relationshipsOxadiazole classClasses of antibioticsLinezolid-resistant S. aureusS. aureusMRSA infectionLead structuresCrystal structureMouse modelIndol-5Lower clearanceExhibit activityAntibioticsSilico dockingBacterium Staphylococcus aureusStaphylococcus aureusInfectionGram-positive bacterium Staphylococcus aureusCell wall biosynthesisPenicillin-binding proteinsGreat promiseAureus
2014
Structure and Cell Wall Cleavage by Modular Lytic Transglycosylase MltC of Escherichia coli
Artola-Recolons C, Lee M, Bernardo-García N, Blázquez B, Hesek D, Bartual S, Mahasenan K, Lastochkin E, Pi H, Boggess B, Meindl K, Usón I, Fisher J, Mobashery S, Hermoso J. Structure and Cell Wall Cleavage by Modular Lytic Transglycosylase MltC of Escherichia coli. ACS Chemical Biology 2014, 9: 2058-2066. PMID: 24988330, PMCID: PMC4168783, DOI: 10.1021/cb500439c.Peer-Reviewed Original ResearchConceptsTwo-domain structureLytic transglycosylasesCell wall assemblyEscherichia coliEssential bacterial enzymeResolution X-ray structureÅ resolution X-ray structureGram-negative bacterium Escherichia coliBacterium Escherichia coliBacterial cell wallCell wall analoguesBacterial genomesGlycan strandsGenomic analysisActive siteCell wallBacterial enzymesFunctional roleSoluble constructWall assemblyGenomeTransglycosylasesExolytic cleavageX-ray structurePeptidoglycanDiscovery of a New Class of Non-β-lactam Inhibitors of Penicillin-Binding Proteins with Gram-Positive Antibacterial Activity
O’Daniel P, Peng Z, Pi H, Testero S, Ding D, Spink E, Leemans E, Boudreau M, Yamaguchi T, Schroeder V, Wolter W, Llarrull L, Song W, Lastochkin E, Kumarasiri M, Antunes N, Espahbodi M, Lichtenwalter K, Suckow M, Vakulenko S, Mobashery S, Chang M. Discovery of a New Class of Non-β-lactam Inhibitors of Penicillin-Binding Proteins with Gram-Positive Antibacterial Activity. Journal Of The American Chemical Society 2014, 136: 3664-3672. PMID: 24517363, PMCID: PMC3985699, DOI: 10.1021/ja500053x.Peer-Reviewed Original ResearchConceptsMethicillin-resistant Staphylococcus aureusPenicillin-binding protein 2aLinezolid-resistant methicillin-resistant Staphylococcus aureusNon-β-lactam antibioticsGlobal public health concernSerious global public health concernPublic health concernClasses of antibioticsMouse modelVivo efficacyOral bioavailabilityProtein 2ABactericidal activityGram-positive antibacterial activityStaphylococcus aureusNon-β-lactam inhibitorsInfectionPenicillin binding proteinsAntibioticsAntibacterial activityVancomycinCharacterization of a selective inhibitor for matrix metalloproteinase-8 (MMP-8)
Ding D, Lichtenwalter K, Pi H, Mobashery S, Chang M. Characterization of a selective inhibitor for matrix metalloproteinase-8 (MMP-8). RSC Medicinal Chemistry 2014, 5: 1381-1383. DOI: 10.1039/c4md00172a.Peer-Reviewed Original Research
2013
A Chemical Biological Strategy to Facilitate Diabetic Wound Healing
Gooyit M, Peng Z, Wolter W, Pi H, Ding D, Hesek D, Lee M, Boggess B, Champion M, Suckow M, Mobashery S, Chang M. A Chemical Biological Strategy to Facilitate Diabetic Wound Healing. ACS Chemical Biology 2013, 9: 105-110. PMID: 24053680, PMCID: PMC3947039, DOI: 10.1021/cb4005468.Peer-Reviewed Original ResearchReactions of All Escherichia coli Lytic Transglycosylases with Bacterial Cell Wall
Lee M, Hesek D, Llarrull L, Lastochkin E, Pi H, Boggess B, Mobashery S. Reactions of All Escherichia coli Lytic Transglycosylases with Bacterial Cell Wall. Journal Of The American Chemical Society 2013, 135: 3311-3314. PMID: 23421439, PMCID: PMC3645847, DOI: 10.1021/ja309036q.Peer-Reviewed Original Research