Heng Zhao
Associate Research ScientistAbout
Research
Publications
2025
Typhoid toxin causes neuropathology by disrupting the blood–brain barrier
Zhao H, Catarino J, Stack G, Albizu A, Lara-Tejero M, Horvath T, Galán J. Typhoid toxin causes neuropathology by disrupting the blood–brain barrier. Nature Microbiology 2025, 10: 1340-1351. PMID: 40341334, DOI: 10.1038/s41564-025-02000-z.Peer-Reviewed Original ResearchConceptsTyphoid toxinTyphoid feverBlood-brain barrierBlood brain barrier disruption in vivoDisruption in vivoManifestations of typhoid feverVirulence factorsSalmonella typhiCatalytic subunitBlood-brain barrier permeability changesToxin actionLife-threatening complicationsSevere neurological manifestationsTyphoidIn vitro modelToxinNeurological complicationsGlial cellsTherapeutic interventionsFeverToxin exposureVirulenceComplicationsNeuropathologyEncephalopathy
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 upregulationRodAMreBHFtsWHomologCellsPeptidoglycanAutolysin
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 observations
2016
Depletion of Undecaprenyl Pyrophosphate Phosphatases Disrupts Cell Envelope Biogenesis in Bacillus subtilis
Zhao H, Sun Y, Peters J, Gross C, Garner E, Helmann J. Depletion of Undecaprenyl Pyrophosphate Phosphatases Disrupts Cell Envelope Biogenesis in Bacillus subtilis. Journal Of Bacteriology 2016, 198: 2925-2935. PMID: 27528508, PMCID: PMC5055597, DOI: 10.1128/jb.00507-16.Peer-Reviewed Original ResearchConceptsUndecaprenyl pyrophosphateCRISPRi systemCell envelope stress responseSynthetic lethal gene pairsTranscriptional repression systemWall teichoic acid synthesisBacillus subtilisEnvelope stress responseCell envelope biogenesisCell envelope synthesisSet of genesLipid II cycleLipid-linked precursorsShort palindromic repeats (CRISPR) systemTeichoic acid synthesisPalindromic repeats systemWall teichoic acidBacterial cell envelopeHigh turgor pressureGenetic redundancyEnvelope biogenesisEssential genesLipid phosphataseRepression systemFunctional redundancy
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
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