Michael Niederweis

Michael Niederweis
Professor

Scientist (C), Center for AIDS Research , School of Medicine
Scientist (C), Center for Biophysical Sciences and Engineering (CBSE) , School of Optometry
Professor (P), Microbiology , Academic Joint Departments

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 Envelope. Chemical Reviews. 121:5124-5157. 2021
2021	Stable polymer bilayers for protein channel recordings at high guanidinium chloride concentrations. Biophysical Journal. 120:1537-1541. 2021
2020	Cryo-EM structure of arabinosyltransferase EmbB from Mycobacterium smegmatis. Nature Communications. 11. 2020
2020	Plasma membrane damage causes NLRP3 activation and pyroptosis during Mycobacterium tuberculosis infection. Nature Communications. 11. 2020
2020	Recognition of an α-helical hairpin in P22 large terminase by a synthetic antibody fragment. Acta Crystallographica. Section d, Structural Biology. 76:876-888. 2020
2020	Cryo-EM Structures and Regulation of Arabinofuranosyltransferase AftD from Mycobacteria. Molecular Cell. 78:683-699.e11. 2020
2020	Photoactivatable Glycolipid Probes for Identifying Mycolate-Protein Interactions in Live Mycobacteria. Journal of the American Chemical Society. 142:7725-7731. 2020
2020	Comprehensive analysis of iron utilization by Mycobacterium tuberculosis. PLoS Pathogens. 16. 2020
2020	NAD hydrolysis by the tuberculosis necrotizing toxin induces lethal oxidative stress in macrophages. Cellular Microbiology. 22. 2020
2019	Heme and hemoglobin utilization by Mycobacterium tuberculosis. Nature Communications. 10. 2019
2019	A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity. Genes. 10. 2019
2019	A humanized yeast phenomic model of deoxycytidine kinase to predict genetic buffering of nucleoside analog cytotoxicity 2019
2019	The tuberculosis necrotizing toxin is an NAD and NADP glycohydrolase with distinct enzymatic properties. Journal of Biological Chemistry. 294:3024-3036. 2019
2019	A Protein Complex from Human Milk Enhances the Activity of Antibiotics and Drugs against Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy. 63. 2019
2018	Cytomegalovirus promotes intestinal macrophage-mediated mucosal inflammation through induction of Smad7. Mucosal Immunology. 11:1694-1704. 2018
2018	NAD⁺ Depletion Triggers Macrophage Necroptosis, a Cell Death Pathway Exploited by Mycobacterium tuberculosis. Cell Reports. 24:429-440. 2018
2017	PPE surface proteins are required for heme utilization by Mycobacterium tuberculosis. mBio. 8. 2017
2016	A Macrophage Infection Model to Predict Drug Efficacy Against Mycobacterium Tuberculosis. ASSAY and Drug Development Technologies. 14:345-354. 2016
2016	Hetero-oligomeric MspA pores in Mycobacterium smegmatis. FEMS Microbiology Letters. 363. 2016
2016	Protein phosphatase, Mg²⁺/Mn²⁺-dependent 1A controls the innate antiviral and antibacterial response of macrophages during HIV-1 and Mycobacterium tuberculosis infection. Oncotarget. 7:15394-15409. 2016
2016	Separable roles for Mycobacterium tuberculosis ESX-3 effectors in iron acquisition and virulence 2016
2015	The tuberculosis necrotizing toxin kills macrophages by hydrolyzing NAD 2015
2015	Surface hydrolysis of sphingomyelin by the outer membrane protein Rv0888 supports replication of Mycobacterium tuberculosis in macrophages 2015
2015	Disulfiram and copper ions kill Mycobacterium tuberculosis in a synergistic manner. Antimicrobial Agents and Chemotherapy. 59:4835-4844. 2015
2015	The mycobacterium tuberculosis outer membrane channel protein CpnT confers susceptibility to toxic molecules. Antimicrobial Agents and Chemotherapy. 59:2328-2336. 2015
2015	Mycobacteria, metals, and the macrophage. Immunological Reviews. 264:249-263. 2015
2014	An outer membrane channel protein of Mycobacterium tuberculosis with exotoxin activity 2014
2014	Role of the Mce1 transporter in the lipid homeostasis of Mycobacterium tuberculosis. Tuberculosis. 94:170-177. 2014
2014	Self-poisoning of Mycobacterium tuberculosis by interrupting siderophore recycling 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 therapy. Frontiers in Immunology. 5. 2014
2013	Porins increase copper susceptibility of Mycobacterium tuberculosis. Journal of Bacteriology. 195:5133-5140. 2013
2013	A multicopper oxidase is required for copper resistance in mycobacterium tuberculosis. Journal of Bacteriology. 195:3724-3733. 2013
2013	Mycobacterium tuberculosis is resistant to streptolydigin. Tuberculosis. 93:401-404. 2013
2013	Copper-boosting compounds: A novel concept for antimycobacterial drug discovery. Antimicrobial Agents and Chemotherapy. 57:1089-1091. 2013
2013	Discovery of a Siderophore Export System Essential for Virulence of Mycobacterium tuberculosis. PLoS Pathogens. 9. 2013
2013	Updating and curating metabolic pathways of TB. Tuberculosis. 93:47-59. 2013
2012	Ectoine biosynthesis in Mycobacterium smegmatis. Applied 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 sequence. ACS Nano. 6:6960-6968. 2012
2012	MspA nanopores from subunit dimers. PLoS ONE. 7. 2012
2012	Cathepsin G and neutrophil elastase contribute to lung-protective immunity against mycobacterial infections in mice. Journal of Immunology. 188:4476-4487. 2012
2012	Resistance mechanisms of Mycobacterium tuberculosis against phagosomal copper overload. Tuberculosis. 92:202-210. 2012
2012	Reading DNA at single-nucleotide resolution with a mutant MspA nanopore and phi29 DNA polymerase. Nature Biotechnology. 30:349-353. 2012
2012	Elucidation and chemical modulation of sulfolipid-1 biosynthesis in Mycobacterium tuberculosis. Journal of Biological Chemistry. 287:7990-8000. 2012
2012	Uptake of sulfate but not phosphate by Mycobacterium tuberculosis is slower than that for Mycobacterium smegmatis. Journal 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
2012	Biological Nanopore MspA for DNA Sequencing. Biophysical Journal. 102:203a-203a. 2012
2011	Nucleotide discrimination with DNA immobilized in the MSPA nanopore. PLoS ONE. 6. 2011
2011	Expression of the ompATb operon accelerates ammonia secretion and adaptation of Mycobacterium tuberculosis to acidic environments 2011
2011	Importance of porins for biocide efficacy against Mycobacterium smegmatis. Applied and Environmental Microbiology. 77:3068-3073. 2011
2011	Mycobacterium tuberculosis can utilize heme as an iron source. Journal of Bacteriology. 193:1767-1770. 2011
2011	Structure and Interactions of the M. tuberculosis Membrane Protein Virulence Factor Rv0899. Biophysical Journal. 100:8a-8a. 2011
2011	Copper resistance is essential for virulence of Mycobacterium tuberculosis 2011
2010	Role of porins in iron uptake by Mycobacterium smegmatis. Journal of Bacteriology. 192:6411-6417. 2010
2010	Antimycobacterial activity in vitro of pigments isolated from Antarctic bacteria 2010
2010	Taking phage integration to the next level as a genetic tool for mycobacteria. Gene. 468:8-19. 2010
2010	Nanopore DNA sequencing with MspA 2010
2010	Hit-and-run stimulation: A novel concept to reactivate latent HIV-1 infection without cytokine gene induction. Journal of Virology. 84:8712-8720. 2010
2010	Mycobacterium tuberculosis Rv0899 Adopts a Mixed α/β-Structure and Does Not Form a Transmembrane β-Barrel. Biochemistry. 49:2768-2777. 2010
2010	Mycobacterial outer membranes: in search of proteins. Trends 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 terrae. Applied and Environmental Microbiology. 76:546-554. 2010
2010	Single Nucleotide Discrimination in Single Stranded DNA Immobilized within Biological Nanopore MspA. Biophysical Journal. 98:600a-600a. 2010
2010	Structure of the Mycobacterium Tuberculosis Virulence Factor Rv0899 (ompATb). Biophysical Journal. 98:624a-625a. 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 smegmatis 2009
2009	Decreased outer membrane permeability protects mycobacteria from killing by ubiquitin-derived peptides 2009
2009	Porins facilitate nitric oxide-mediated killing of mycobacteria 2009
2009	Functions of the periplasmic loop of the porin MspA from Mycobacterium smegmatis. Journal of Biological Chemistry. 284:10223-10231. 2009
2009	Direct observation of gold nanoparticle assemblies with the porin MspA on mica. ACS Nano. 3:462-466. 2009
2009	Nanopore Sequencing with MspA. Biophysical Journal. 96:316a-316a. 2009
2009	Physiology of Mycobacteria. Advances in Microbial Physiology. 55. 2009
2009	Role of porins in the susceptibility of Mycobacterium smegmatis and Mycobacterium chelonae to aldehyde-based disinfectants and drugs. Antimicrobial Agents and Chemotherapy. 53:4015-4018. 2009
2008	Single-molecule DNA detection with an engineered MspA protein nanopore 2008
2008	Identification of outer membrane proteins of Mycobacterium tuberculosis. Tuberculosis. 88:526-544. 2008
2008	Role of porins for uptake of antibiotics by Mycobacterium smegmatis. Antimicrobial Agents and Chemotherapy. 52:3127-3134. 2008
2008	Identification of a novel multidrug efflux pump of Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy. 52:2503-2511. 2008
2008	Rv1698 of Mycobacterium tuberculosis represents a new class of channel-forming outer membrane proteins. Journal of Biological Chemistry. 283:17827-17837. 2008
2008	Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structure 2008
2008	Nutrient acquisition by mycobacteria.. Microbiology. 154:679-692. 2008
2008	Construction of unmarked deletion mutants in mycobacteria. Methods in Molecular Biology. 465:279-295. 2008
2007	Functional expression of the Flp recombinase in Mycobacterium bovis BCG. Gene. 399:112-119. 2007
2007	A genomic view of sugar transport in Mycobacterium smegmatis and Mycobacterium tuberculosis. Journal of Bacteriology. 189:5903-5915. 2007
2007	Identification of two Mycobacterium smegmatis lipoproteins exported by a SecA2-dependent pathway. Journal of Bacteriology. 189:5090-5100. 2007
2007	Characterization of nanostructured surfaces generated by reconstitution of the porin MspA from Mycobacterium smegmatis. Small. 3:1084-1097. 2007
2007	Porins are required for uptake of phosphates by Mycobacterium smegmatis. Journal of Bacteriology. 189:2435-2442. 2007
2007	Expression of the major porin gene mspA is regulated in Mycobacterium smegmatis. Journal of Bacteriology. 189:958-967. 2007
2006	Nanoarray-surfaces by reconstitution of the porin MspA into stabilized long-chain-lipid-monolayers at a gold-surface. Electroanalysis. 18:1859-1870. 2006
2006	Topology of the porin MspA in the outer membrane of Mycobacterium smegmatis. Journal of Biological Chemistry. 281:5908-5915. 2006
2006	P6.26 GFP-Based Rapid Detection of the Mycobactericidal Efficacy of Disinfectants in the Quantitative Carrier Test prEN 14563. Journal of Hospital Infection. 64:S39-S39. 2006
2005	The growth rate of Mycobacterium smegmatis depends on sufficient porin-mediated influx of nutrients 2005
2005	Erratum: MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatis (Molecular Microbiology (2001) 40 (451-464)) 2005
2005	Porins limit the intracellular persistence of Mycobacterium smegmatis. Microbiology. 151:2403-2410. 2005
2004	Consecutive gene deletions in Mycobacterium smegmatis using the yeast FLP recombinase. Gene. 343:181-190. 2004
2004	Identification and semi-quantitative analysis of Mycobacterium tuberculosis H37Rv ftsZ gene-specific promoter activity-containing regions. Research in Microbiology. 155:817-826. 2004
2004	DNA-free RNA preparations from mycobacteria. BMC Microbiology. 4. 2004
2004	Multidrug resistance of a porin deletion mutant of Mycobacterium smegmatis. Antimicrobial 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 cells. British Journal of Haematology. 125:167-179. 2004
2004	The MspA porin promotes growth and increases antibiotic susceptibility of both Mycobacterium bovis BCG and Mycobacterium tuberculosis.. Microbiology. 150:853-864. 2004
2004	The Structure of a Mycobacterial Outer-Membrane Channel. Science. 303:1189-1192. 2004
2004	Efficient eukaryotic expression of fluorescent scFv fusion proteins directed against CD antigens for FACS applications. Journal of Immunological Methods. 285:265-280. 2004
2004	Reconstitution of a porin from Mycobacterium smegmatis at HOPG covered with hydrophobic host layers. Surface and Interface Analysis. 36:127-134. 2004
2004	The MspA porin promotes growth and increases antibiotic susceptibility of both Mycobacterium bovis BCG and Mycobacterium tuberculosis. Microbiology. 150:853-864. 2004
2003	The Phosphotransferase System of Streptomyces coelicolor Is Biased for N-Acetylglucosamine Metabolism. Journal of Bacteriology. 185:7019-7023. 2003
2003	Mycobacterial porins - New channel proteins in unique outer membranes 2003
2003	High-level expression of the mycobacterial porin MspA in Escherichia coli and purification of the recombinant protein 2003
2003	The core of the tetrameric mycobacterial porin MspA is an extremely stable β-sheet domain. Journal 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 Surfaces 2002
2002	A tetrameric porin limits the cell wall permeability of Mycobacterium smegmatis. Journal of Biological Chemistry. 277:37567-37572. 2002
2001	Energy transfer between fluorescent proteins using a co-expression system in Mycobacterium smegmatis. Gene. 278:115-124. 2001
2001	Nanostructuring of Carbon Surfaces by Deposition of a Channel-Forming Protein and Subsequent Polymerization of Methyl Methacrylate Prepolymers 2001
2001	Characterization of four members of a multigene family encoding outer membrane proteins of Helicobacter pylori and their potential for vaccination 2001
2001	Modular organization of the AIDA autotransporter translocator: The N-terminal β1-domain is surface-exposed and stabilizes the transmembrane β2-domain 2001
2001	MspA provides the main hydrophilic pathway through the cell wall of Mycobacterium smegmatis 2001
2000	Selective extraction and purification of a mycobacterial outer membrane protein. Analytical Biochemistry. 285:113-120. 2000
2000	The FtsH protein accumulates at the septum of Bacillus subtilis during cell division and sporulation. Journal of Bacteriology. 182:3870-3873. 2000
2000	Quantitative analysis of gene expression with an improved green fluorescent protein 2000
2000	Permeation of tetracyclines through membranes of liposomes and Escherichia coli 2000
1999	Cloning of the mspA gene encoding a porin from Mycobacterium smegmatis 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
1999	Porins in the cell wall of Mycobacterium tuberculosis. Journal of Bacteriology. 181:6543-6546. 1999
1998	Biochemical and biophysical characterization of the cell wall porin of Corynebacterium glutamicum: The channel is formed by a low molecular mass polypeptide. Biochemistry. 37:15024-15032. 1998
1995	Identification of channel-forming activity in the cell wall of Corynebacterium glutamicum. Journal 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 phased. Nucleic Acids Research. 22:1562-1566. 1994
1994	Matrix effects suggest an important influence of DNA-polyacrylamide interactions on the electrophoretic mobility of DNA. Journal of Biological Chemistry. 269:10156-10162. 1994
1993	Synthesis of 8-Bromo- and 8-Azido-2’-Deoxyadenosine-5’-O-(1-Thiotriphosphate) 1993
1993	Electrophoretic analysis of protein‐induced DNA bending and twist changes. ELECTROPHORESIS. 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 decamers. Journal of Molecular Biology. 228:322-326. 1992
	A type VII secretion system in Group B Streptococcus mediates cytotoxicity and virulence
	Stable Polymer Bilayers for Protein Channel Recordings at High Guanidinium Chloride Concentrations