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
    2021 Transporters Involved in the Biogenesis and Functionalization of the Mycobacterial Cell EnvelopeChemical Reviews.  121:5124-5157. 2021
    2021 Stable polymer bilayers for protein channel recordings at high guanidinium chloride concentrationsBiophysical Journal.  120:1537-1541. 2021
    2020 Recognition of an α-helical hairpin in P22 large terminase by a synthetic antibody fragmentActa Crystallographica. Section d, Structural Biology.  76:876-888. 2020
    2020 NAD hydrolysis by the tuberculosis necrotizing toxin induces lethal oxidative stress in macrophagesCellular Microbiology.  22. 2020
    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
    2018 NAD+ Depletion Triggers Macrophage Necroptosis, a Cell Death Pathway Exploited by Mycobacterium tuberculosisCell Reports.  24:429-440. 2018
    2016 A Macrophage Infection Model to Predict Drug Efficacy Against Mycobacterium TuberculosisASSAY and Drug Development Technologies.  14:345-354. 2016
    2016 Hetero-oligomeric MspA pores in Mycobacterium smegmatisFEMS Microbiology Letters.  363. 2016
    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
    2013 Copper-boosting compounds: A novel concept for antimycobacterial drug discoveryAntimicrobial Agents and Chemotherapy.  57:1089-1091. 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 Biological Nanopore MspA for DNA SequencingBiophysical Journal.  102:203a-203a. 2012
    2011 Importance of porins for biocide efficacy against Mycobacterium smegmatisApplied and Environmental Microbiology.  77:3068-3073. 2011
    2011 Structure and Interactions of the M. tuberculosis Membrane Protein Virulence Factor Rv0899Biophysical Journal.  100:8a-8a. 2011
    2010 Antimycobacterial activity in vitro of pigments isolated from Antarctic bacteria 2010
    2010 Mycobacterium tuberculosis Rv0899 Adopts a Mixed α/β-Structure and Does Not Form a Transmembrane β-BarrelBiochemistry.  49:2768-2777. 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
    2010 Single Nucleotide Discrimination in Single Stranded DNA Immobilized within Biological Nanopore MspABiophysical Journal.  98:600a-600a. 2010
    2010 Structure of the Mycobacterium Tuberculosis Virulence Factor Rv0899 (ompATb)Biophysical Journal.  98:624a-625a. 2010
    2009 Direct observation of gold nanoparticle assemblies with the porin MspA on micaACS Nano.  3:462-466. 2009
    2009 Nanopore Sequencing with MspABiophysical Journal.  96:316a-316a. 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 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
    2006 Nanoarray-surfaces by reconstitution of the porin MspA into stabilized long-chain-lipid-monolayers at a gold-surfaceElectroanalysis.  18:1859-1870. 2006
    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
    2001 Modular organization of the AIDA autotransporter translocator: The N-terminal β1-domain is surface-exposed and stabilizes the transmembrane β2-domain 2001
    2000 Selective extraction and purification of a mycobacterial outer membrane proteinAnalytical Biochemistry.  285:113-120. 2000
    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
    1993 Electrophoretic analysis of protein‐induced DNA bending and twist changesELECTROPHORESIS.  14:693-698. 1993
    A type VII secretion system in Group B Streptococcus mediates cytotoxicity and virulence
    Control of subunit stoichiometry in single-chain MspA nanopores
    Stable Polymer Bilayers for Protein Channel Recordings at High Guanidinium Chloride Concentrations

    Chapter

    Year Title Altmetric
    2008 Experimental strategies toward the use of the porin MspA as a nanotemplate and for biosensors.  19-39. 2008
    Mycobacterial Porins.  153-165.

    Principal Investigator On

  • Characterization of a Mycobacterium Tuberculosis Porin with an Autotransporter-Like Toxin Activity  awarded by American Lung Association
  • Copper Transport in Mycobacterium Tuberculosis  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Heme and Hemoglobin Utilization by Mycobacterium Tuberculosis  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Killing and Sensitizing Bacterial Pathogens to Conventional Antibiotics Using a Protein Complex From Human Milk  awarded by UNIVERSITY OF LUND, SWEDEN
  • M. Tuberculosis Membrane Protein Pharmaceutical Targets  awarded by Florida State University
  • Nanopore Sequencing of DNA with MspA  awarded by UNIVERSITY OF WASHINGTON
  • Nanopore Sequencing of DNA with MspA  awarded by UNIVERSITY OF WASHINGTON
  • Self-Poisoning of Mycobacterium Tuberculosis by Inhibiting Siderophore Secretion  awarded by TRES CANTOS OPEN LAB FOUNDATION
  • Siderophore Secretion by Mycobacterium Tuberculosis  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Siderophore-Dependent Inhibitors of Mycobacterium Tuberculosis  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • Single-chain MspA for Nanopore Sequencing of DNA  awarded by National Human Genome Research Institute/NIH/DHHS
  • The Interactions Network of the Outer Membrane Copper Efflux Channel Protein MctB of M. Tuberculosis  awarded by New York Community Trust
  • The Necrosis-Inducing Toxin of Mycobacterium Tuberculosis  awarded by National Institute of Allergy and Infectious Diseases/NIH/DHHS
  • 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