Hualiang Pi, PhD
Assistant ProfessorCards
About
Research
Overview
Clostridioides difficile is a Gram-positive, spore-forming anaerobe and the leading cause of healthcare-associated and antibiotic-related intestinal infections in the United States. In the Pi Lab, we take a multidisciplinary approach—combining genetics, biochemistry, structural biology, advanced imaging, and animal infection models—to investigate this important gut pathogen. Our research is primarily focused on uncovering the microbial stress defense strategies that enable C. difficile to colonize and persist within the host during infection.
Medical Research Interests
Bacterial Infections; Host Microbial Interactions; Organelle Biogenesis
Publications
2025
The extracytoplasmic sigma factor σX supports biofilm formation and increases biocontrol efficacy in Bacillus velezensis 118
Cai Y, Tao H, Gaballa A, Pi H, Helmann J. The extracytoplasmic sigma factor σX supports biofilm formation and increases biocontrol efficacy in Bacillus velezensis 118. Scientific Reports 2025, 15: 5315. PMID: 39939707, PMCID: PMC11822112, DOI: 10.1038/s41598-025-89284-7.Peer-Reviewed Original ResearchConceptsPlant growth-promoting rhizobacteriaBiocontrol efficacyBiocontrol activityIncrease biocontrol efficacyReduced biocontrol efficacyEffect of Bacillus sppFusarium wilt of bananaWilt of bananaGrowth-promoting rhizobacteriaColonize plant rootsExtracytoplasmic functionBiocontrol agentsBiofilm formationEnhancing crop productivityPlant rootsPromoting rhizobacteriaBiocontrolLipopeptide productionFusarium wiltRoot colonizationSoil isolatesReduced biofilm formationSigX mutantSwarming motilityCrop productionBPS2025 - Molecular mechanism of ferrosome formation
Sun R, Mao Z, Pi H, Mei J, Luo F, Skaar E, Zhou Q. BPS2025 - Molecular mechanism of ferrosome formation. Biophysical Journal 2025, 124: 67a. DOI: 10.1016/j.bpj.2024.11.430.Peer-Reviewed Original Research
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
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Pi Lab
840 West Campus Drive , Advanced Biosciences Center 215
West Haven, CT 06516
United States
Pi Lab
Shipping Address, 300 Heffernan Drive, ABC Rm 215
West Haven, CT 06516
United States