Schnappinger, Dirk

Publications

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selected publications

Weak links: Advancing target-based drug discovery by identifying the most vulnerable targets. Annals of the New York Academy of Sciences. 2024 Review GET IT
Inhibitors of the Thioesterase Activity of Mycobacterium tuberculosis Pks13 Discovered Using DNA-Encoded Chemical Library Screening. ACS infectious diseases. 2024 Academic Article GET IT
CpsA mediates infection of recruited lung myeloid cells by Mycobacterium tuberculosis. Cell reports. 2023 Academic Article GET IT
Synthetic lethality of Mycobacterium tuberculosis NADH dehydrogenases is due to impaired NADH oxidation. mBio. 2023 Academic Article GET IT
A "suicide" BCG strain provides enhanced immunogenicity and robust protection against Mycobacterium tuberculosis in macaques. 2023 GET IT
Development of an Engineered Mycobacterium tuberculosis Strain for a Safe and Effective Tuberculosis Human Challenge Model. 2023 GET IT
Identification and Optimization of Novel Inhibitors of the Polyketide Synthase 13 Thioesterase Domain with Antitubercular Activity. Journal of medicinal chemistry. 2023 Academic Article GET IT
Metabolically distinct roles of NAD synthetase and NAD kinase define the essentiality of NAD and NADP in Mycobacterium tuberculosis. mBio. 2023 Academic Article GET IT
Polyfluorinated salicylic acid analogs do not interfere with siderophore biosynthesis. Tuberculosis (Edinburgh, Scotland). 2023 Academic Article GET IT
Cyclic AMP is a critical mediator of intrinsic drug resistance and fatty acid metabolism in M. tuberculosis. eLife. 2023 Academic Article GET IT
Lysyl-tRNA synthetase, a target for urgently needed M. tuberculosis drugs. Nature communications. 2022 Academic Article GET IT
CRISPRi chemical genetics and comparative genomics identify genes mediating drug potency in Mycobacterium tuberculosis. Nature microbiology. 2022 Academic Article GET IT
Spiropyrimidinetrione DNA Gyrase Inhibitors with Potent and Selective Antituberculosis Activity. Journal of medicinal chemistry. 2022 Academic Article GET IT
CinA mediates multidrug tolerance in Mycobacterium tuberculosis. Nature communications. 2022 Academic Article GET IT
Times cited: 16
Chemical-genetic interaction mapping links carbon metabolism and cell wall structure to tuberculosis drug efficacy. Proceedings of the National Academy of Sciences of the United States of America. 2022 Academic Article GET IT
Host-pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice. eLife. 2022 Academic Article GET IT
Optimization of TAM16, a Benzofuran That Inhibits the Thioesterase Activity of Pks13; Evaluation toward a Preclinical Candidate for a Novel Antituberculosis Clinical Target. Journal of medicinal chemistry. 2021 Academic Article GET IT
Multiple acyl-CoA dehydrogenase deficiency kills Mycobacterium tuberculosis in vitro and during infection. Nature communications. 2021 Academic Article GET IT
An improved statistical method to identify chemical-genetic interactions by exploiting concentration-dependence. PloS one. 2021 Academic Article GET IT
Genome-wide gene expression tuning reveals diverse vulnerabilities of M. tuberculosis. Cell. 2021 Academic Article GET IT
Times cited: 96
Genetic models of latent tuberculosis in mice reveal differential influence of adaptive immunity. The Journal of experimental medicine. 2021 Academic Article GET IT
Times cited: 6
Spirocycle MmpL3 Inhibitors with Improved hERG and Cytotoxicity Profiles as Inhibitors of Mycobacterium tuberculosis Growth. ACS omega. 2021 Academic Article GET IT
Times cited: 17
Rediscovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in Mycobacterium tuberculosis. The Journal of biological chemistry. 2021 Academic Article GET IT
Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies. Journal of medicinal chemistry. 2021 Academic Article GET IT
Times cited: 9
Re-discovery of PF-3845 as a new chemical scaffold inhibiting phenylalanyl-tRNA synthetase in Mycobacterium tuberculosis. The Journal of biological chemistry. 2021 Academic Article GET IT
Two-Way Regulation of MmpL3 Expression Identifies and Validates Inhibitors of MmpL3 Function in Mycobacterium tuberculosis. ACS infectious diseases. 2020 Academic Article GET IT
Dual inhibition of the terminal oxidases eradicates antibiotic-tolerant Mycobacterium tuberculosis. EMBO molecular medicine. 2020 Academic Article GET IT
Times cited: 43
Depletion of the DarG antitoxin in Mycobacterium tuberculosis triggers the DNA-damage response and leads to cell death. Molecular microbiology. 2020 Academic Article GET IT
Times cited: 17
Tissue Distribution of Doxycycline in Animal Models of Tuberculosis. Antimicrobial agents and chemotherapy. 2020 Academic Article GET IT
Times cited: 16
Persistent Mycobacterium tuberculosis infection in mice requires PerM for successful cell division. eLife. 2019 Academic Article GET IT
Times cited: 11
Statistical analysis of variability in TnSeq data across conditions using zero-inflated negative binomial regression. BMC bioinformatics. 2019 Academic Article GET IT
Times cited: 12
Plasticity of the Mycobacterium tuberculosis respiratory chain and its impact on tuberculosis drug development. Nature communications. 2019 Academic Article GET IT
Times cited: 67
Large-scale chemical-genetics yields new M. tuberculosis inhibitor classes. Nature. 2019 Academic Article GET IT
Times cited: 40
An NAD⁺ Phosphorylase Toxin Triggers Mycobacterium tuberculosis Cell Death. Molecular cell. 2019 Academic Article GET IT
Times cited: 52
Investigation of ( S)-(-)-Acidomycin: A Selective Antimycobacterial Natural Product That Inhibits Biotin Synthase. ACS infectious diseases. 2019 Academic Article GET IT
Times cited: 20
Opposing reactions in coenzyme A metabolism sensitize Mycobacterium tuberculosis to enzyme inhibition. Science (New York, N.Y.). 2019 Academic Article GET IT
Times cited: 50
Discovery and Structure-Activity-Relationship Study of N-Alkyl-5-hydroxypyrimidinone Carboxamides as Novel Antitubercular Agents Targeting Decaprenylphosphoryl-β-d-ribose 2'-Oxidase. Journal of medicinal chemistry. 2018 Academic Article GET IT
Times cited: 28
Identification of Enolase as the Target of 2-Aminothiazoles in Mycobacterium tuberculosis. Frontiers in microbiology. 2018 Academic Article GET IT
Times cited: 7
Metabolic principles of persistence and pathogenicity in Mycobacterium tuberculosis. Nature reviews. Microbiology. 2018 Review GET IT
Times cited: 131
Targeting protein biotinylation enhances tuberculosis chemotherapy. Science translational medicine. 2018 Academic Article GET IT
Times cited: 21
Avoiding Antibiotic Inactivation in Mycobacterium tuberculosis by Rv3406 through Strategic Nucleoside Modification. ACS infectious diseases. 2018 Academic Article GET IT
Times cited: 12
Conformationally Constrained Cinnolinone Nucleoside Analogues as Siderophore Biosynthesis Inhibitors for Tuberculosis. ACS medicinal chemistry letters. 2018 Academic Article GET IT
Times cited: 23
Critical Impact of Peptidoglycan Precursor Amidation on the Activity of l,d-Transpeptidases from Enterococcus faecium and Mycobacterium tuberculosis. Chemistry (Weinheim an der Bergstrasse, Germany). 2018 Academic Article GET IT
Times cited: 14
Chemical Genetic Interaction Profiling Reveals Determinants of Intrinsic Antibiotic Resistance in Mycobacterium tuberculosis. Antimicrobial agents and chemotherapy. 2017 Academic Article GET IT
Times cited: 62
Structure-Based Optimization of Pyridoxal 5'-Phosphate-Dependent Transaminase Enzyme (BioA) Inhibitors that Target Biotin Biosynthesis in Mycobacterium tuberculosis. Journal of medicinal chemistry. 2017 Academic Article GET IT
Times cited: 30
Depleting Mycobacterium tuberculosis of the transcription termination factor Rho causes pervasive transcription and rapid death. Nature communications. 2017 Academic Article GET IT
Times cited: 45
Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation in Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America. 2017 Academic Article GET IT
Times cited: 70
Programmable transcriptional repression in mycobacteria using an orthogonal CRISPR interference platform. Nature microbiology. 2017 Academic Article GET IT
Times cited: 295
Comprehensive Essentiality Analysis of the Mycobacterium tuberculosis Genome via Saturating Transposon Mutagenesis. mBio. 2017 Academic Article GET IT
Times cited: 369
A broader spectrum of tuberculosis. Nature medicine. 2016 Comment GET IT
Times cited: 8
Validation of CoaBC as a Bactericidal Target in the Coenzyme A Pathway of Mycobacterium tuberculosis. ACS infectious diseases. 2016 Academic Article GET IT
Times cited: 56
Therapeutic Potential of the Mycobacterium tuberculosis Mycolic Acid Transporter, MmpL3. Antimicrobial agents and chemotherapy. 2016 Academic Article GET IT
Times cited: 94
Mycobacterium tuberculosis Thioredoxin Reductase Is Essential for Thiol Redox Homeostasis but Plays a Minor Role in Antioxidant Defense. PLoS pathogens. 2016 Academic Article GET IT
Times cited: 47
Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis. Nature communications. 2016 Academic Article GET IT
Times cited: 48
Targeting Mycobacterium tuberculosis Biotin Protein Ligase (MtBPL) with Nucleoside-Based Bisubstrate Adenylation Inhibitors. Journal of medicinal chemistry. 2015 Academic Article GET IT
Times cited: 37
Fragment-based exploration of binding site flexibility in Mycobacterium tuberculosis BioA. Journal of medicinal chemistry. 2015 Academic Article GET IT
Times cited: 28
Disruption of an M. tuberculosis membrane protein causes a magnesium-dependent cell division defect and failure to persist in mice. PLoS pathogens. 2015 Academic Article GET IT
Times cited: 27
Stressed mycobacteria use the chaperone ClpB to sequester irreversibly oxidized proteins asymmetrically within and between cells. Cell host & microbe. 2015 Academic Article GET IT
Times cited: 75
Construction of conditional knockdown mutants in mycobacteria. Methods in molecular biology (Clifton, N.J.). 2015 Academic Article GET IT
Times cited: 27
Target-based identification of whole-cell active inhibitors of biotin biosynthesis in Mycobacterium tuberculosis. Chemistry & biology. 2014 Academic Article GET IT
Times cited: 43
Inactivation of fructose-1,6-bisphosphate aldolase prevents optimal co-catabolism of glycolytic and gluconeogenic carbon substrates in Mycobacterium tuberculosis. PLoS pathogens. 2014 Academic Article GET IT
Times cited: 59
Triosephosphate isomerase is dispensable in vitro yet essential for Mycobacterium tuberculosis to establish infection. mBio. 2014 Academic Article GET IT
Times cited: 40
Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis. PLoS pathogens. 2014 Academic Article GET IT
Times cited: 57
Mycobacterium tuberculosis exploits asparagine to assimilate nitrogen and resist acid stress during infection. PLoS pathogens. 2014 Academic Article GET IT
Times cited: 121
Regulated Expression Systems for Mycobacteria and Their Applications. Microbiology spectrum. 2014 Academic Article GET IT
Regulated expression systems for mycobacteria and their applications. Microbiology Spectrum. 2014 Article GET IT
Bisubstrate Inhibitors of Biotin Protein Ligase in Mycobacterium tuberculosis Resistant to Cyclonucleoside Formation. ACS medicinal chemistry letters. 2013 Academic Article GET IT
Times cited: 31
A genetic strategy to identify targets for the development of drugs that prevent bacterial persistence. Proceedings of the National Academy of Sciences of the United States of America. 2013 Academic Article GET IT
Times cited: 110
Database resources for the tuberculosis community. Tuberculosis (Edinburgh, Scotland). 2013 Information Resource GET IT
Times cited: 24
Bisubstrate adenylation inhibitors of biotin protein ligase from Mycobacterium tuberculosis. Chemistry & biology. 2011 Academic Article GET IT
Times cited: 76
Mechanism-based inactivation by aromatization of the transaminase BioA involved in biotin biosynthesis in Mycobaterium tuberculosis. Journal of the American Chemical Society. 2011 Academic Article GET IT
Times cited: 36
Evaluating the sensitivity of Mycobacterium tuberculosis to biotin deprivation using regulated gene expression. PLoS pathogens. 2011 Academic Article GET IT
Times cited: 120
Glycolytic and non-glycolytic functions of Mycobacterium tuberculosis fructose-1,6-bisphosphate aldolase, an essential enzyme produced by replicating and non-replicating bacilli. The Journal of biological chemistry. 2011 Academic Article GET IT
Times cited: 69
The Mycobacterium tuberculosis β-oxidation genes echA5 and fadB3 are dispensable for growth in vitro and in vivo. Tuberculosis (Edinburgh, Scotland). 2011 Academic Article GET IT
Times cited: 26
Depletion of antibiotic targets has widely varying effects on growth. Proceedings of the National Academy of Sciences of the United States of America. 2011 Academic Article GET IT
Times cited: 128
Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes. Cell host & microbe. 2011 Academic Article GET IT
Times cited: 98
Simultaneous analysis of multiple Mycobacterium tuberculosis knockdown mutants in vitro and in vivo. PloS one. 2010 Academic Article GET IT
Times cited: 59
Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity. PloS one. 2010 Academic Article GET IT
Times cited: 117
Protein inactivation in mycobacteria by controlled proteolysis and its application to deplete the beta subunit of RNA polymerase. Nucleic acids research. 2010 Academic Article GET IT
Times cited: 75
Nitrate respiration protects hypoxic Mycobacterium tuberculosis against acid- and reactive nitrogen species stresses. PloS one. 2010 Academic Article GET IT
Times cited: 87
Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection. Proceedings of the National Academy of Sciences of the United States of America. 2010 Academic Article GET IT
Times cited: 276
The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nature reviews. Microbiology. 2009 Review GET IT
Times cited: 1085
Improved tetracycline repressors for gene silencing in mycobacteria. Nucleic acids research. 2009 Academic Article GET IT
Times cited: 79
Acid-susceptible mutants of Mycobacterium tuberculosis share hypersusceptibility to cell wall and oxidative stress and to the host environment. Journal of bacteriology. 2008 Academic Article GET IT
Times cited: 126
A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis. Nature medicine. 2008 Academic Article GET IT
Times cited: 269
Biosynthesis and recycling of nicotinamide cofactors in mycobacterium tuberculosis. An essential role for NAD in nonreplicating bacilli. The Journal of biological chemistry. 2008 Academic Article GET IT
Times cited: 138
In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice. Nature medicine. 2007 Academic Article GET IT
Times cited: 211
Mycobacterial nonhomologous end joining mediates mutagenic repair of chromosomal double-strand DNA breaks. Journal of bacteriology. 2007 Academic Article GET IT
Times cited: 77
Silencing Mycobacterium smegmatis by using tetracycline repressors. Journal of bacteriology. 2007 Academic Article GET IT
Times cited: 98
Mycobacterium tuberculosis virulence: lipids inside and out. Nature medicine. 2007 Article GET IT
Times cited: 41
Genomics of host-pathogen interactions. Progress in drug research. Fortschritte der Arzneimittelforschung. Progres des recherches pharmaceutiques. 2007 Information Resource GET IT
Times cited: 4
Controlling gene expression in mycobacteria. Future microbiology. 2006 Review GET IT
Times cited: 22
Introduction: genomic approaches in infectious diseases. Microbes and infection. 2006 Editorial Article GET IT
Ancestral antibiotic resistance in Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America. 2005 Academic Article GET IT
Times cited: 254
Controlling gene expression in mycobacteria with anhydrotetracycline and Tet repressor. Nucleic acids research. 2005 Academic Article GET IT
Times cited: 281
Regulation of the Mycobacterium tuberculosis PE/PPE genes. Tuberculosis (Edinburgh, Scotland). 2004 Academic Article GET IT
Times cited: 108
MyD88 primes macrophages for full-scale activation by interferon-gamma yet mediates few responses to Mycobacterium tuberculosis. The Journal of experimental medicine. 2003 Academic Article GET IT
Times cited: 125
Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. The Journal of experimental medicine. 2003 Academic Article GET IT
Times cited: 792
Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment. The Journal of experimental medicine. 2003 Academic Article GET IT
Times cited: 1182
Single-chain Tet transregulators. Nucleic acids research. 2003 Academic Article GET IT
Times cited: 38
Isolation of plasmids from E. coli by alkaline lysis. Methods in molecular biology (Clifton, N.J.). 2003 Academic Article GET IT
Times cited: 17
Isolation of plasmids from E. coli by boiling lysis. Methods in molecular biology (Clifton, N.J.). 2003 Academic Article GET IT
Times cited: 1
Energy transfer between fluorescent proteins using a co-expression system in Mycobacterium smegmatis. Gene. 2001 Academic Article GET IT
Times cited: 52
Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase. The Journal of experimental medicine. 2001 Academic Article GET IT
Times cited: 402
Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha -crystallin. Proceedings of the National Academy of Sciences of the United States of America. 2001 Academic Article GET IT
Times cited: 649
Identification of a stability determinant on the edge of the Tet repressor four-helix bundle dimerization motif. Biochemistry. 2001 Academic Article GET IT
Times cited: 11
Functional Genomics of Mycobacterium tuberculosis Using DNA Microarrays. Methods in molecular medicine. 2001 Academic Article GET IT
Whole genome DNA microarray expression analysis of biofilm development by Vibrio cholerae O1 E1 Tor. Methods in enzymology. 2001 Academic Article GET IT
Times cited: 39
Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system. Nature structural biology. 2000 Academic Article GET IT
Times cited: 356
Solvent-exposed residues in the Tet repressor (TetR) four-helix bundle contribute to subunit recognition and dimer stability. The Journal of biological chemistry. 1999 Academic Article GET IT
Times cited: 12
Generation of conditional mutants in higher eukaryotes by switching between the expression of two genes. Proceedings of the National Academy of Sciences of the United States of America. 1999 Academic Article GET IT
Times cited: 95
Crystal structure of the tet repressor in complex with a novel tetracycline, 9-(N,N-dimethylglycylamido)- 6-demethyl-6-deoxy-tetracycline. Journal of molecular biology. 1999 Academic Article GET IT
Times cited: 35
Conformational changes necessary for gene regulation by Tet repressor assayed by reversible disulfide bond formation. The EMBO journal. 1998 Academic Article GET IT
Conformational changes of the Tet repressor induced by tetracycline trapping. Journal of molecular biology. 1998 Academic Article GET IT
Times cited: 98
Determinants of protein-protein recognition by four helix bundles: changing the dimerization specificity of Tet repressor. The EMBO journal. 1998 Academic Article GET IT
Times cited: 38
Crystallization and preliminary X-ray analysis of the Tet-repressor/operator complex. Acta crystallographica. Section D, Biological crystallography. 1998 Academic Article GET IT
Times cited: 8
The role of the variable region in Tet repressor for inducibility by tetracycline. The Journal of biological chemistry. 1997 Academic Article GET IT
Times cited: 21
Fast large-scale purification of tetracycline repressor variants from overproducing Escherichia coli strains. Journal of chromatography. A. 1996 Academic Article GET IT
Times cited: 46
Extracellular expression of native human anti-lysozyme fragments in Staphylococcus carnosus. FEMS microbiology letters. 1995 Academic Article GET IT
Times cited: 16

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Research

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Co-investigator Network

Funding awarded

Gene inactivation and modulation of Mtb targets to build combinations awarded by Bill & Melinda Gates Foundation Principal Investigator 2023 - 2026
Conditional Mtb knockdown mutants for TB drug discovery awarded by Bill & Melinda Gates Foundation Principal Investigator 2023 - 2026
BMGF-funded collaboration with Adapsyn awarded by Adapsyn Bioscience Inc Principal Investigator 2023 - 2025

Determinants of TB control, relapse and reinfection awarded by National Institute of Allergy & Infectious Diseases Co-Investigator 2021 - 2026
Pathway Analysis in Tuberculosis awarded by National Institute of Allergy & Infectious Diseases Co-Investigator 2020 - 2025
Conditional Expression of Mycobacterial Genes awarded by National Institute of Allergy & Infectious Diseases Co-Investigator 2018 - 2024

M. tuberculosis carbon metabolism during infection awarded by National Institute of Allergy & Infectious Diseases Co-Principal Investigator 2023 - 2028
Development of a self inactivating, highly effective TB vaccine awarded by National Institute of Allergy & Infectious Diseases Co-Principal Investigator 2019 - 2024

Conditionally Replicating Mycobacterium Tuberculosis Vaccines awarded by National Institute of Allergy & Infectious Diseases Key Personnel 2018 - 2024

Chemical Genomics of Tuberculosis Principal Investigator Subaward 2022 - 2025
missing activity Principal Investigator Subaward 2019 - 2023

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Background

education and training

Ph.D., University of Erlangen (Germany) 1998

Contact

full name

Dirk Schnappinger

primary email

dis2003@med.cornell.edu

VIVO Weill Cornell Medical College

Dirk Schnappinger Professor of Microbiology and Immunology

Publications

selected publications

Research

Funding awarded

Background

education and training

Contact

full name

primary email

Phone

Publications

selected publications

Research

Funding awarded

Background

education and training

Contact

full name

primary email