Positions

Overview

  • One of the most prominent features of M. tuberculosis is its unusual outer membrane that plays a crucial role in the intrinsic drug resistance and in survival of M. tuberculosis in vivo. This membrane is functionalized by intriguing proteins which provide essential functions such as nutrient uptake, have new structures and likely function by novel mechanisms. We discovered the first outer membrane channel protein in mycobacteria, obtained the first crystal structure of a mycobacterial outer membrane protein and demonstrated that mycobacteria indeed have two membranes. Our goal is to identify and characterize outer membrane proteins of M. tuberculosis. One of those proteins, CpnT, enables the secretion of the major exotoxin of M. tuberculosis, a NAD+ glycohydrolase which triggers necroptosis in infected macrophages. We use state-of-the art genetic, biochemical and biophysical approaches to achieve our aims.
  • Selected Publications

    Academic Article

    Year Title Altmetric
    2019 A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicityGenes.  10. 2019
    2019 A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity 2019
    2019 A Protein Complex from Human Milk Enhances the Activity of Antibiotics and Drugs against Mycobacterium tuberculosisAntimicrobial Agents and Chemotherapy.  63. 2019
    2019 NAD hydrolysis by the tuberculosis necrotizing toxin induces lethal oxidative stress in macrophagesCellular Microbiology2019
    2019 The tuberculosis necrotizing toxin is an NAD and NADP glycohydrolase with distinct enzymatic propertiesJournal of Biological Chemistry.  294:3024-3036. 2019
    2018 NAD+ Depletion Triggers Macrophage Necroptosis, a Cell Death Pathway Exploited by Mycobacterium tuberculosisCell Reports.  24:429-440. 2018
    2017 PPE surface proteins are required for heme utilization by Mycobacterium tuberculosismBio.  8. 2017
    2016 A Macrophage Infection Model to Predict Drug Efficacy Against Mycobacterium TuberculosisASSAY and Drug Development Technologies.  14:345-354. 2016
    2016 Protein phosphatase, Mg2+/Mn2+-dependent 1A controls the innate antiviral and antibacterial response of macrophages during HIV-1 and Mycobacterium tuberculosis infectionOncotarget.  7:15394-15409. 2016
    2016 Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulenceProceedings of the National Academy of Sciences.  113:E348-E357. 2016
    2016 Hetero-oligomeric MspA pores in Mycobacterium smegmatisFEMS Microbiology Letters.  363. 2016
    2015 The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NADNature Structural Biology.  22:672-678. 2015
    2015 Surface hydrolysis of sphingomyelin by the outer membrane protein Rv0888 supports replication of Mycobacterium tuberculosis in macrophagesMicrobiological sciences.  97:881-897. 2015
    2015 Disulfiram and copper ions kill Mycobacterium tuberculosis in a synergistic mannerAntimicrobial Agents and Chemotherapy.  59:4835-4844. 2015
    2015 The mycobacterium tuberculosis outer membrane channel protein CpnT confers susceptibility to toxic moleculesAntimicrobial Agents and Chemotherapy.  59:2328-2336. 2015
    2015 Mycobacteria, metals, and the macrophageImmunological Reviews.  264:249-263. 2015
    2014 An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activityProceedings of the National Academy of Sciences.  111:6750-6755. 2014
    2014 Role of the Mce1 transporter in the lipid homeostasis of Mycobacterium tuberculosisTuberculosis.  94:170-177. 2014
    2014 Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recyclingProceedings of the National Academy of Sciences.  111:1945-1950. 2014
    2014 Organ pathology in the absence of bacteria?Journal of Infectious Diseases.  209:971. 2014
    2014 The progression of cell death affects the rejection of allogeneic tumors in immune-competent mice - implications for cancer therapyFrontiers in Immunology.  5. 2014
    2013 Porins increase copper susceptibility of Mycobacterium tuberculosisJournal of Bacteriology.  195:5133-5140. 2013
    2013 A multicopper oxidase is required for copper resistance in mycobacterium tuberculosisJournal of Bacteriology.  195:3724-3733. 2013
    2013 Mycobacterium tuberculosis is resistant to streptolydiginTuberculosis.  93:401-404. 2013
    2013 Copper-boosting compounds: A novel concept for antimycobacterial drug discoveryAntimicrobial Agents and Chemotherapy.  57:1089-1091. 2013
    2013 Discovery of a Siderophore Export System Essential for Virulence of Mycobacterium tuberculosisPLoS Pathogens.  9. 2013
    2013 Updating and curating metabolic pathways of TBTuberculosis.  93:47-59. 2013
    2012 Ectoine biosynthesis in Mycobacterium smegmatisApplied and Environmental Microbiology.  78:7483-7486. 2012
    2012 Molecular dynamics study of MspA arginine mutants predicts slow DNA translocations and ion current blockades indicative of DNA sequenceACS Nano.  6:6960-6968. 2012
    2012 MspA nanopores from subunit dimersPLoS ONE.  7. 2012
    2012 Cathepsin G and neutrophil elastase contribute to lung-protective immunity against mycobacterial infections in miceJournal of Immunology.  188:4476-4487. 2012
    2012 Resistance mechanisms of Mycobacterium tuberculosis against phagosomal copper overloadTuberculosis.  92:202-210. 2012
    2012 Reading DNA at single-nucleotide resolution with a mutant MspA nanopore and phi29 DNA polymeraseNature Biotechnology.  30:349-353. 2012
    2012 Elucidation and chemical modulation of sulfolipid-1 biosynthesis in Mycobacterium tuberculosisJournal of Biological Chemistry.  287:7990-8000. 2012
    2012 Uptake of sulfate but not phosphate by Mycobacterium tuberculosis is slower than that for Mycobacterium smegmatisJournal of Bacteriology.  194:956-964. 2012
    2012 Molecular structure and peptidoglycan recognition of mycobacterium tuberculosis ArfA (Rv0899)Journal of Molecular Biology.  416:208-220. 2012
    2011 Nucleotide discrimination with DNA immobilized in the MSPA nanoporePLoS ONE.  6. 2011
    2011 Expression of the ompATb operon accelerates ammonia secretion and adaptation of Mycobacterium tuberculosis to acidic environmentsMicrobiological sciences.  80:900-918. 2011
    2011 Importance of porins for biocide efficacy against Mycobacterium smegmatisApplied and Environmental Microbiology.  77:3068-3073. 2011
    2011 Mycobacterium tuberculosis can utilize heme as an iron sourceJournal of Bacteriology.  193:1767-1770. 2011
    2011 Copper resistance is essential for virulence of Mycobacterium tuberculosisProceedings of the National Academy of Sciences.  108:1621-1626. 2011
    2010 Role of porins in iron uptake by Mycobacterium smegmatisJournal of Bacteriology.  192:6411-6417. 2010
    2010 Antimycobacterial activity in vitro of pigments isolated from Antarctic bacteriaAntonie van Leeuwenhoek.  98:531-540. 2010
    2010 Taking phage integration to the next level as a genetic tool for mycobacteriaGene.  468:8-19. 2010
    2010 Nanopore DNA sequencing with MspAProceedings of the National Academy of Sciences.  107:16060-16065. 2010
    2010 Hit-and-run stimulation: A novel concept to reactivate latent HIV-1 infection without cytokine gene inductionJournal of Virology.  84:8712-8720. 2010
    2010 Mycobacterium tuberculosis Rv0899 Adopts a Mixed α/β-Structure and Does Not Form a Transmembrane β-BarrelBiochemistry.  49:2768-2777. 2010
    2010 Mycobacterial outer membranes: in search of proteinsTrends in Microbiology.  18:109-116. 2010
    2010 Rapid evaluation of the Mycobactericidal efficacy of disinfectants in the quantitative carrier test EN 14563 by using fluorescent Mycobacterium terraeApplied and Environmental Microbiology.  76:546-554. 2010
    2009 Construction of unmarked deletion mutants in mycobacteria.Methods in Molecular Biology.  465:279-295. 2009
    2009 Poly-N-Isopropyl-acrylamide/acrylic acid copolymers for the generation of nanostructures on mica surfaces and as hydrophobic host systems for the porin mspa from mycobacterium smegmatisJournal of Physical Chemistry C.  113:16485-16494. 2009
    2009 Decreased outer membrane permeability protects mycobacteria from killing by ubiquitin-derived peptidesMicrobiological sciences.  73:844-857. 2009
    2009 Porins facilitate nitric oxide-mediated killing of mycobacteriaMicrobes and Infection.  11:868-875. 2009
    2009 Functions of the periplasmic loop of the porin MspA from Mycobacterium smegmatisJournal of Biological Chemistry.  284:10223-10231. 2009
    2009 Direct observation of gold nanoparticle assemblies with the porin MspA on micaACS Nano.  3:462-466. 2009
    2009 Physiology of MycobacteriaAdvances in Microbial Physiology.  55. 2009
    2009 Role of porins in the susceptibility of Mycobacterium smegmatis and Mycobacterium chelonae to aldehyde-based disinfectants and drugsAntimicrobial Agents and Chemotherapy.  53:4015-4018. 2009
    2008 Single-molecule DNA detection with an engineered MspA protein nanoporeProceedings of the National Academy of Sciences.  105:20647-20652. 2008
    2008 Identification of outer membrane proteins of Mycobacterium tuberculosisTuberculosis.  88:526-544. 2008
    2008 Role of porins for uptake of antibiotics by Mycobacterium smegmatisAntimicrobial Agents and Chemotherapy.  52:3127-3134. 2008
    2008 Identification of a novel multidrug efflux pump of Mycobacterium tuberculosisAntimicrobial Agents and Chemotherapy.  52:2503-2511. 2008
    2008 Rv1698 of Mycobacterium tuberculosis represents a new class of channel-forming outer membrane proteinsJournal of Biological Chemistry.  283:17827-17837. 2008
    2008 Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structureProceedings of the National Academy of Sciences.  105:3963-3967. 2008
    2008 Nutrient acquisition by mycobacteria.Microbiology.  154:679-692. 2008
    2008 Construction of unmarked deletion mutants in mycobacteriaMethods in Molecular Biology.  465:279-295. 2008
    2007 Functional expression of the Flp recombinase in Mycobacterium bovis BCGGene.  399:112-119. 2007
    2007 A genomic view of sugar transport in Mycobacterium smegmatis and Mycobacterium tuberculosisJournal of Bacteriology.  189:5903-5915. 2007
    2007 Identification of two Mycobacterium smegmatis lipoproteins exported by a SecA2-dependent pathwayJournal of Bacteriology.  189:5090-5100. 2007
    2007 Characterization of nanostructured surfaces generated by reconstitution of the porin MspA from Mycobacterium smegmatisSmall.  3:1084-1097. 2007
    2007 Porins are required for uptake of phosphates by Mycobacterium smegmatisJournal of Bacteriology.  189:2435-2442. 2007
    2007 Expression of the major porin gene mspA is regulated in Mycobacterium smegmatisJournal of Bacteriology.  189:958-967. 2007
    2006 Nanoarray-surfaces by reconstitution of the porin MspA into stabilized long-chain-lipid-monolayers at a gold-surfaceElectroanalysis.  18:1859-1870. 2006
    2006 Topology of the porin MspA in the outer membrane of Mycobacterium smegmatisJournal of Biological Chemistry.  281:5908-5915. 2006
    2005 The growth rate of Mycobacterium smegmatis depends on sufficient porin-mediated influx of nutrientsMicrobiological sciences.  58:714-730. 2005
    2005 Erratum: MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatis (Molecular Microbiology (2001) 40 (451-464))Microbiological sciences.  57:1509. 2005
    2005 Porins limit the intracellular persistence of Mycobacterium smegmatisMicrobiology.  151:2403-2410. 2005
    2004 Consecutive gene deletions in Mycobacterium smegmatis using the yeast FLP recombinaseGene.  343:181-190. 2004
    2004 Identification and semi-quantitative analysis of Mycobacterium tuberculosis H37Rv ftsZ gene-specific promoter activity-containing regionsResearch in Microbiology.  155:817-826. 2004
    2004 DNA-free RNA preparations from mycobacteriaBMC Microbiology.  4. 2004
    2004 Multidrug resistance of a porin deletion mutant of Mycobacterium smegmatisAntimicrobial Agents and Chemotherapy.  48:4163-4170. 2004
    2004 A recombinant bispecific single-chain Fv antibody against HLA class II and FcγRIII (CD16) triggers effective lysis of lymphoma cellsBritish Journal of Haematology.  125:167-179. 2004
    2004 The Structure of a Mycobacterial Outer-Membrane ChannelScience.  303:1189-1192. 2004
    2004 Efficient eukaryotic expression of fluorescent scFv fusion proteins directed against CD antigens for FACS applicationsJournal of Immunological Methods.  285:265-280. 2004
    2004 Reconstitution of a porin from Mycobacterium smegmatis at HOPG covered with hydrophobic host layersSurface and Interface Analysis.  36:127-134. 2004
    2004 The MspA porin promotes growth and increases antibiotic susceptibility of both Mycobacterium bovis BCG and Mycobacterium tuberculosisMicrobiology.  150:853-864. 2004
    2003 The Phosphotransferase System of Streptomyces coelicolor Is Biased for N-Acetylglucosamine MetabolismJournal of Bacteriology.  185:7019-7023. 2003
    2003 Mycobacterial porins - New channel proteins in unique outer membranesMicrobiological sciences.  49:1167-1177. 2003
    2003 High-level expression of the mycobacterial porin MspA in Escherichia coli and purification of the recombinant proteinJournal of chromatography. B, Biomedical sciences and applications.  790:337-348. 2003
    2003 The core of the tetrameric mycobacterial porin MspA is an extremely stable β-sheet domainJournal of Biological Chemistry.  278:8678-8685. 2003
    2003 Purification of porins from Mycobacterium smegmatis.Methods in Molecular Biology.  228:139-150. 2003
    2002 Nanostructuring by Deposition of Protein Channels Formed on Carbon SurfacesNano Letters.  2:1263-1268. 2002
    2002 A tetrameric porin limits the cell wall permeability of Mycobacterium smegmatisJournal of Biological Chemistry.  277:37567-37572. 2002
    2001 Energy transfer between fluorescent proteins using a co-expression system in Mycobacterium smegmatisGene.  278:115-124. 2001
    2001 Nanostructuring of Carbon Surfaces by Deposition of a Channel-Forming Protein and Subsequent Polymerization of Methyl Methacrylate PrepolymersNano Letters.  1:169-174. 2001
    2001 Characterization of four members of a multigene family encoding outer membrane proteins of Helicobacter pylori and their potential for vaccinationMicrobes and Infection.  3:171-179. 2001
    2001 Modular organization of the AIDA autotransporter translocator: The N-terminal β1-domain is surface-exposed and stabilizes the transmembrane β2-domainAntonie van Leeuwenhoek.  80:19-34. 2001
    2001 MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatisMicrobiological sciences.  40:451-464. 2001
    2000 Selective extraction and purification of a mycobacterial outer membrane proteinAnalytical Biochemistry.  285:113-120. 2000
    2000 The FtsH protein accumulates at the septum of Bacillus subtilis during cell division and sporulationJournal of Bacteriology.  182:3870-3873. 2000
    2000 Quantitative analysis of gene expression with an improved green fluorescent proteinEuropean Journal of Biochemistry.  267:1565-1570. 2000
    2000 Permeation of tetracyclines through membranes of liposomes and Escherichia coliEuropean Journal of Biochemistry.  267:527-534. 2000
    1999 Porins in the cell wall of Mycobacterium tuberculosisJournal of Bacteriology.  181:6543-6546. 1999
    1999 Cloning of the mspA gene encoding a porin from Mycobacterium smegmatisMicrobiological sciences.  33:933-945. 1999
    1999 Erratum: Porins in the cell wall of Mycobacterium tuberculosis (Journal of Bacteriology (1999) 181:20 (6543-6546))Journal of Bacteriology.  181:7650. 1999
    1998 Biochemical and biophysical characterization of the cell wall porin of Corynebacterium glutamicum: The channel is formed by a low molecular mass polypeptideBiochemistry.  37:15024-15032. 1998
    1995 Identification of channel-forming activity in the cell wall of Corynebacterium glutamicumJournal of Bacteriology.  177:5716-5718. 1995
    1994 Oligo[d(C) · (G)] runs exhibit a helical repeat of 11.1 bp in solution and cause slight DNA curvature when properly phasedNucleic Acids Research.  22:1562-1566. 1994
    1994 Matrix effects suggest an important influence of DNA-polyacrylamide interactions on the electrophoretic mobility of DNAJournal of Biological Chemistry.  269:10156-10162. 1994
    1993 Synthesis of 8-Bromo- and 8-Azido-2’-Deoxyadenosine-5’-O-(1-Thiotriphosphate)Nucleosides and Nucleotides.  12:757-771. 1993
    1993 Electrophoretic analysis of protein‐induced DNA bending and twist changesELECTROPHORESIS.  14:693-698. 1993
    1992 An accurate method for determining the helical repeat of DNA in solution reveals differences to the crystal structures of two B-DNA decamersJournal of Molecular Biology.  228:322-326. 1992

    Chapter

    Year Title Altmetric
    2008 Experimental strategies toward the use of the porin MspA as a nanotemplate and for biosensors.  19-39. 2008

    Teaching Activities

  • GBS760 - Prokar Gene and Mole Bio (Spring Term 2018) 2018
  • GBSC720 - Journal Club 2 (Fall Term 2017) 2017
  • UNIV398 - Undergraduate Research (Fall Term 2017) 2017
  • GBS760 - Prokar Gene and Mole Bio (Spring Term 2017) 2017
  • GBSC720 - Journal Club 2 (Spring Term 2017) 2017
  • UNIV398 - Undergraduate Research (Spring Term 2017) 2017
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2016) 2016
  • UNIV398 - Undergraduate Research (Fall Term 2016) 2016
  • GBS760 - Prokar Gene and Mole Bio (Spring Term 2016) 2016
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2016) 2016
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2015) 2015
  • GBS760 - Prokar Gene and Mole Bio (Spring Term 2015) 2015
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2015) 2015
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2014) 2014
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2014) 2014
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2013) 2013
  • GBS760 - Prokar Gene and Mole Bio (Spring Term 2013) 2013
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2013) 2013
  • GBS708 - Basic Genetics/Mole BIo (Fall Term 2012) 2012
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2012) 2012
  • GBS708 - CORE COURSE II: GENETICS/MOLECULAR BIOLOGY (Fall Term 2012) 2012
  • GBS760 - Prokar Gene and Mole Bio (Spring Term 2012) 2012
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2012) 2012
  • GBS708 - Basic Genetics/Mole BIo (Fall Term 2011) 2011
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2011) 2011
  • GBS708 - CORE COURSE II: GENETICS/MOLECULAR BIOLOGY (Fall Term 2011) 2011
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2011) 2011
  • GBS708 - Basic Genetics/Mole BIo (Fall Term 2010) 2010
  • GBS760 - Prokar Gene and Mole Bio (Fall Term 2010) 2010
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2010) 2010
  • GBS708 - CORE COURSE II: GENETICS/MOLECULAR BIOLOGY (Fall Term 2010) 2010
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2010) 2010
  • CMB720 - CMB II Genes (Fall Term 2009) 2009
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2009) 2009
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2009) 2009
  • CMB720 - CMB II Genes (Fall Term 2008) 2008
  • MIC712 - Phys and Path of Mycobacteria (Fall Term 2008) 2008
  • MIC712 - Phys and Path of Mycobacteria (Spring Term 2008) 2008
  • Education And Training

  • Doctor of Philosophy in Microbiology, Friedrich-Alexander University of Erlangen-Nuremberg 1993
  • Full Name

  • Michael Niederweis