Featured Publications
An essential periplasmic protein coordinates lipid trafficking and is required for asymmetric polar growth in mycobacteria
Gupta K, Gwin C, Rahlwes K, Biegas K, Wang C, Park J, Liu J, Swarts B, Morita Y, Rego E. An essential periplasmic protein coordinates lipid trafficking and is required for asymmetric polar growth in mycobacteria. ELife 2022, 11: e80395. PMID: 36346214, PMCID: PMC9678360, DOI: 10.7554/elife.80395.Peer-Reviewed Original ResearchConceptsPeriplasmic proteinsPolar growthNew cell wall materialOld poleQuantitative time-lapse imagingAsymmetric polar growthCell wall synthesisCell envelope compositionCell wall materialTime-lapse imagingCellular asymmetryEssential proteinsBacterial geneticsEssential transporterSingle geneWall synthesisLipid traffickingPopulation of cellsPlasma membraneTMM transportUnknown functionBroad functionsMycolic acidsTrehalose monomycolateEnvelope compositionItaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella
Chen M, Sun H, Boot M, Shao L, Chang SJ, Wang W, Lam TT, Lara-Tejero M, Rego EH, Galán JE. Itaconate is an effector of a Rab GTPase cell-autonomous host defense pathway against Salmonella. Science 2020, 369: 450-455. PMID: 32703879, PMCID: PMC8020367, DOI: 10.1126/science.aaz1333.Peer-Reviewed Original ResearchMaturing 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 crosslinksElongationGrowthMaintenanceTargetDeletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity
Rego E, Audette R, Rubin E. Deletion of a mycobacterial divisome factor collapses single-cell phenotypic heterogeneity. Nature 2017, 546: 153-157. PMID: 28569798, PMCID: PMC5567998, DOI: 10.1038/nature22361.Peer-Reviewed Original ResearchNonlinear structured-illumination microscopy with a photoswitchable protein reveals cellular structures at 50-nm resolution
Rego EH, Shao L, Macklin JJ, Winoto L, Johansson GA, Kamps-Hughes N, Davidson MW, Gustafsson MG. Nonlinear structured-illumination microscopy with a photoswitchable protein reveals cellular structures at 50-nm resolution. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 109: e135-e143. PMID: 22160683, PMCID: PMC3271870, DOI: 10.1073/pnas.1107547108.Peer-Reviewed Original ResearchConceptsStructured-illumination microscopyUltralow light intensitiesSuperresolution imaging methodExcited statesFluorophore excited stateStructured illumination microscopyLight intensityRequired nonlinearityResolution extensionHigh light intensityActin cytoskeletonCellular structureReversible photoswitchingNuclear poresNonlinear responseIllumination intensitySuch nonlinear responsesPhotoswitchable proteinsSpatial resolutionFluorescent proteinBiological samplesSix-orderImaging methodMicroscopyPolystyrene beadsSuper-resolution 3D microscopy of live whole cells using structured illumination
Shao L, Kner P, Rego EH, Gustafsson MG. Super-resolution 3D microscopy of live whole cells using structured illumination. Nature Methods 2011, 8: 1044-1046. PMID: 22002026, DOI: 10.1038/nmeth.1734.Peer-Reviewed Original ResearchA nucleoid-associated protein is involved in the emergence of antibiotic resistance by promoting the frequent exchange of the replicative DNA polymerase in Mycobacterium smegmatis
Ng W, Rego E. A nucleoid-associated protein is involved in the emergence of antibiotic resistance by promoting the frequent exchange of the replicative DNA polymerase in Mycobacterium smegmatis. MSphere 2024, 9: e00122-24. PMID: 38591887, PMCID: PMC11237743, DOI: 10.1128/msphere.00122-24.Peer-Reviewed Original ResearchNucleoid-associated proteinsReplicative DNA polymerasesBypass DNA lesionsDNA replicationDNA polymeraseAntibiotic resistanceDamaged DNAExpression of error-prone DNA polymerasesReplicative polymerasesHigh-fidelity replicative polymerasesQuantitative fluorescence imaging techniqueError-prone DNA synthesisDNA lesionsError-prone DNA polymerasesHorizontal gene transferEmergence of antibiotic resistanceDNA-damaging agentsRepair damaged DNAResistance to rifampinRobust cell growthGrowth defectLsr2Replication forksBacterial speciesChromosomal mutations
2024
Phenotypic Heterogeneity in Pathogens.
Sherry J, Rego E. Phenotypic Heterogeneity in Pathogens. Annual Review Of Genetics 2024 PMID: 39083846, DOI: 10.1146/annurev-genet-111523-102459.Peer-Reviewed Original ResearchPhenotypic heterogeneityGenetically identical populationSalmonella typhimurium</i>Genetic diversityPathogen diversityPathogen populationsBacterial pathogensPathogen subpopulationsGenetic heterogeneityInvading pathogensHost organismFluctuating environmentsInfectious disease progressionPathogensIdentical populationsTreatment escapeInfection outcomesHeterogeneous subpopulationsDisease progressionInfecting organismDiversityCausative linkGeneticsSubpopulationsPhenotype
2022
Mycobacterial 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 ResearchConceptsCell 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 ResearchConceptsPenicillin 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
2020
Fighting microbial pathogens by integrating host ecosystem interactions and evolution
Burmeister AR, Hansen E, Cunningham JJ, Rego EH, Turner PE, Weitz JS, Hochberg ME. Fighting microbial pathogens by integrating host ecosystem interactions and evolution. BioEssays 2020, 43: e2000272. PMID: 33377530, PMCID: PMC9127240, DOI: 10.1002/bies.202000272.Commentaries, Editorials and LettersConceptsField of ecologyEvolutionary biologyHost ecosystemEcosystem interactionsEvolutionary principlesMicrobial pathogensHigh research priorityMicrobial diseasesDisease-causing factorsEcosystemsResearch prioritiesStudy of pathogenesisMultiple interactionsSystems-based approachImportant consequencesComplex networksEcologyBiologyDisease treatmentInteractionPathogensHostSynergistic benefitsEmpirical exampleAreaThe Conserved Translation Factor LepA Is Required for Optimal Synthesis of a Porin Family in Mycobacterium smegmatis
Fishbein S, Tomasi F, Wolf I, Dulberger C, Wang A, Keshishian H, Wallace L, Carr S, Ioerger T, Rego E, Rubin E. The Conserved Translation Factor LepA Is Required for Optimal Synthesis of a Porin Family in Mycobacterium smegmatis. Journal Of Bacteriology 2020, 203: 10.1128/jb.00604-20. PMID: 33361193, PMCID: PMC8095456, DOI: 10.1128/jb.00604-20.Peer-Reviewed Original ResearchMembrane-associated proteinsMembrane homeostasisCellular processesCell wallMembrane-associated proteomeWhole cell proteomeMajor membrane proteinOuter membrane porinsSteady-state abundanceDrug tolerance phenotypeMembrane proteomePorin familyTolerance phenotypeDeletion mutantsMembrane proteinsTranslation factorsMembrane porinsMajor porinsNutrient uptakeCell wall constituentsMycobacterial cell wallAntibiotic tolerancePorinProteomeDrug targets
2019
Drug Susceptibility of Individual Mycobacterial Cells
Boot M, Rego E. Drug Susceptibility of Individual Mycobacterial Cells. 2019, 247-272. DOI: 10.1007/978-3-030-25241-0_11.ChaptersThe Dream of a Mycobacterium
Baranowski C, Rego E, Rubin E. The Dream of a Mycobacterium. 2019, 1096-1106. DOI: 10.1128/9781683670131.ch66.Chapters
2018
Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription
Zhu JH, Wang BW, Pan M, Zeng YN, Rego H, Javid B. Rifampicin can induce antibiotic tolerance in mycobacteria via paradoxical changes in rpoB transcription. Nature Communications 2018, 9: 4218. PMID: 30310059, PMCID: PMC6181997, DOI: 10.1038/s41467-018-06667-3.Peer-Reviewed Original ResearchCharacterization 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
2015
Phosphorylation of the Peptidoglycan Synthase PonA1 Governs the Rate of Polar Elongation in Mycobacteria
Kieser K, Boutte C, Kester J, Baer C, Barczak A, Meniche X, Chao M, Rego E, Sassetti C, Fortune S, Rubin E. Phosphorylation of the Peptidoglycan Synthase PonA1 Governs the Rate of Polar Elongation in Mycobacteria. PLOS Pathogens 2015, 11: e1005010. PMID: 26114871, PMCID: PMC4483258, DOI: 10.1371/journal.ppat.1005010.Peer-Reviewed Original ResearchConceptsPolar growthPenicillin binding proteinsCell elongationMost rod-shaped bacteriaNew cell wall materialTransglycosylase activityNormal cell lengthCell-wall peptidoglycanNew cell wallHuman pathogen Mycobacterium tuberculosisCell lengthRod-shaped bacteriaCell wall materialCell polesCell fitnessPolar elongationPathogen Mycobacterium tuberculosisWall peptidoglycanAntibiotic stressCytoplasmic regionCell wallBinding proteinPonA1Cell growthEnzymatic activity
2014
Practical Structured Illumination Microscopy
Rego EH, Shao L. Practical Structured Illumination Microscopy. Methods In Molecular Biology 2014, 1251: 175-192. PMID: 25391800, DOI: 10.1007/978-1-4939-2080-8_10.Peer-Reviewed Original ResearchQuantitative analysis and modeling of katanin function in flagellar length control
Kannegaard E, Rego E, Schuck S, Feldman J, Marshall W. Quantitative analysis and modeling of katanin function in flagellar length control. Molecular Biology Of The Cell 2014, 25: 3686-3698. PMID: 25143397, PMCID: PMC4230626, DOI: 10.1091/mbc.e14-06-1116.Peer-Reviewed Original ResearchConceptsFlagellar length controlFlagellar lengthCytoplasmic microtubulesFull-length flagellaHalf-length flagellaLength controlPools of tubulinFlagellar assemblyTranscriptional regulationKatanin functionKatanin-mediated severingOrganelle sizeRegulatory subunitChlamydomonas reinhardtiiCandidate genesMicrotubule severingPreexisting poolFlagellaRegulatory systemPrecursor proteinModel systemGenesSimple model systemMicrotubulesMutationsChapter 15 Structured Illumination Microscopy
Shao L, Rego E. Chapter 15 Structured Illumination Microscopy. 2014, 213-225. DOI: 10.1016/b978-0-12-409513-7.00015-4.Peer-Reviewed Original Research