Dirk Schnappinger

Summary

Affiliation: Cornell University
Country: USA

Publications

  1. doi request reprint Construction of conditional knockdown mutants in mycobacteria
    Dirk Schnappinger
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA
    Methods Mol Biol 1285:151-75. 2015
  2. pmc Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment
    Dirk Schnappinger
    Department of Microbiology and Immunology, Cornell University, 1300 York Avenue, New York, NY 10021, USA
    J Exp Med 198:693-704. 2003
  3. ncbi request reprint Genomics of host-pathogen interactions
    Dirk Schnappinger
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, USA
    Prog Drug Res 64:311, 313-43. 2007
  4. ncbi request reprint Expression profiling of host pathogen interactions: how Mycobacterium tuberculosis and the macrophage adapt to one another
    Dirk Schnappinger
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Microbes Infect 8:1132-40. 2006
  5. pmc Acid-susceptible mutants of Mycobacterium tuberculosis share hypersusceptibility to cell wall and oxidative stress and to the host environment
    Omar H Vandal
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10065, USA
    J Bacteriol 191:625-31. 2009
  6. pmc A genetic strategy to identify targets for the development of drugs that prevent bacterial persistence
    Jee Hyun Kim
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065
    Proc Natl Acad Sci U S A 110:19095-100. 2013
  7. pmc Improved tetracycline repressors for gene silencing in mycobacteria
    Marcus Klotzsche
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA
    Nucleic Acids Res 37:1778-88. 2009
  8. pmc Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier
    Kyu Y Rhee
    Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
    Trends Microbiol 19:307-14. 2011
  9. pmc Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes
    Aditya Venugopal
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA
    Cell Host Microbe 9:21-31. 2011
  10. pmc In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice
    Sheetal Gandotra
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA
    Nat Med 13:1515-20. 2007

Research Grants

  1. Alternative Respiratory Chains of M. tuberculosis
    Dirk Schnappinger; Fiscal Year: 2007

Collaborators

Detail Information

Publications35

  1. doi request reprint Construction of conditional knockdown mutants in mycobacteria
    Dirk Schnappinger
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA
    Methods Mol Biol 1285:151-75. 2015
    ....
  2. pmc Transcriptional Adaptation of Mycobacterium tuberculosis within Macrophages: Insights into the Phagosomal Environment
    Dirk Schnappinger
    Department of Microbiology and Immunology, Cornell University, 1300 York Avenue, New York, NY 10021, USA
    J Exp Med 198:693-704. 2003
    ..The microbial transcriptome thus served as a bioprobe of the MTB phagosomal environment, showing it to be nitrosative, oxidative, functionally hypoxic, carbohydrate poor, and capable of perturbing the pathogen's cell envelope...
  3. ncbi request reprint Genomics of host-pathogen interactions
    Dirk Schnappinger
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, USA
    Prog Drug Res 64:311, 313-43. 2007
    ..This chapter describes how these approaches have been applied to the analysis of host-pathogen interactions and discusses how such studies might facilitate the development of new antibiotics...
  4. ncbi request reprint Expression profiling of host pathogen interactions: how Mycobacterium tuberculosis and the macrophage adapt to one another
    Dirk Schnappinger
    Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA
    Microbes Infect 8:1132-40. 2006
    ..This response is shaped by macrophage produced reactive nitrogen and oxygen molecules and affected by viability and virulence of the pathogen...
  5. pmc Acid-susceptible mutants of Mycobacterium tuberculosis share hypersusceptibility to cell wall and oxidative stress and to the host environment
    Omar H Vandal
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10065, USA
    J Bacteriol 191:625-31. 2009
    ..Pathways utilized by M. tuberculosis for acid resistance and intrabacterial pH maintenance are potential targets for chemotherapy...
  6. pmc A genetic strategy to identify targets for the development of drugs that prevent bacterial persistence
    Jee Hyun Kim
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065
    Proc Natl Acad Sci U S A 110:19095-100. 2013
    ....
  7. pmc Improved tetracycline repressors for gene silencing in mycobacteria
    Marcus Klotzsche
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA
    Nucleic Acids Res 37:1778-88. 2009
    ..The new reverse TetRs silence target genes more efficiently and allowed complete phenotypic silencing of M. smegmatis secA1 with chromosomally integrated tetR genes...
  8. pmc Central carbon metabolism in Mycobacterium tuberculosis: an unexpected frontier
    Kyu Y Rhee
    Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
    Trends Microbiol 19:307-14. 2011
    ..Mtb's CCM has thus emerged as a frontier for both fundamental and translational research...
  9. pmc Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes
    Aditya Venugopal
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA
    Cell Host Microbe 9:21-31. 2011
    ..Mtb deficient in both DlaT and PdhC phenocopies Lpd-deficient Mtb. Thus, Mtb critically requires BCKADH along with PDH and PNR/P for pathogenesis. These findings position Lpd as a potential target for anti-infectives against Mtb...
  10. pmc In vivo gene silencing identifies the Mycobacterium tuberculosis proteasome as essential for the bacteria to persist in mice
    Sheetal Gandotra
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA
    Nat Med 13:1515-20. 2007
    ..Conditional gene silencing could therefore facilitate the validation of up to 800 potential Mtb drug targets and improve our understanding of host-pathogen dynamics...
  11. pmc Simultaneous analysis of multiple Mycobacterium tuberculosis knockdown mutants in vitro and in vivo
    Antje Blumenthal
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America
    PLoS ONE 5:e15667. 2010
    ....
  12. ncbi request reprint Isolation of plasmids from E. coli by boiling lysis
    Sabine Ehrt
    Department of Microbiology, Weill Medical College of Cornell University, New York, NY, USA
    Methods Mol Biol 235:79-82. 2003
  13. pmc Mycobacterial survival strategies in the phagosome: defence against host stresses
    Sabine Ehrt
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA
    Cell Microbiol 11:1170-8. 2009
    ..The latter three mechanisms are the focus of this review...
  14. pmc A membrane protein preserves intrabacterial pH in intraphagosomal Mycobacterium tuberculosis
    Omar H Vandal
    Department of Microbiology, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA
    Nat Med 14:849-54. 2008
    ..Thus, Mtb is able to resist acid, owing in large part to Rv3671c, and this resistance is essential for virulence. Disruption of Mtb's acid resistance and intrabacterial pH maintenance systems is an attractive target for chemotherapy...
  15. pmc Controlling gene expression in mycobacteria with anhydrotetracycline and Tet repressor
    Sabine Ehrt
    Department of Microbiology and Immunology, Weill Medical College of Cornell University New York, NY 10021, USA
    Nucleic Acids Res 33:e21. 2005
    ..Finally, we demonstrated that these systems allow gene regulation in M.tuberculosis within the macrophage phagosome...
  16. pmc Silencing Mycobacterium smegmatis by using tetracycline repressors
    Xinzheng V Guo
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10021, USA
    J Bacteriol 189:4614-23. 2007
    ....
  17. pmc Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection
    Joeli Marrero
    Department of Microbiology and Immunology and Department of Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:9819-24. 2010
    ..Mtb thus relies on gluconeogenesis throughout the infection. PEPCK depletion also attenuated Mtb in IFNgamma-deficient mice, suggesting that this enzyme represents an attractive target for chemotherapy...
  18. pmc Inactivation of fructose-1,6-bisphosphate aldolase prevents optimal co-catabolism of glycolytic and gluconeogenic carbon substrates in Mycobacterium tuberculosis
    Susan Puckett
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America
    PLoS Pathog 10:e1004144. 2014
    ..These data thus not only evaluate FBA as a potential drug target in both replicating and persistent Mtb, but also expand our understanding of the multiplicity of in vitro conditions that define the essentiality of Mtb's FBA in vivo. ..
  19. pmc Evaluating the sensitivity of Mycobacterium tuberculosis to biotin deprivation using regulated gene expression
    Sae Woong Park
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America
    PLoS Pathog 7:e1002264. 2011
    ..Moreover, these studies provide an experimental strategy to systematically rank the in vivo value of potential drug targets in Mtb and other pathogens...
  20. pmc Protein inactivation in mycobacteria by controlled proteolysis and its application to deplete the beta subunit of RNA polymerase
    Jee Hyun Kim
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA
    Nucleic Acids Res 39:2210-20. 2011
    ..They further demonstrate that depletion of RpoB by ∼ 93% is sufficient to cause death of M. smegmatis...
  21. pmc Genome-wide screen for Mycobacterium tuberculosis genes that regulate host immunity
    Aimee M Beaulieu
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America
    PLoS ONE 5:e15120. 2010
    ..The mutant list provides a platform for exploring the immunobiology of tuberculosis, for example, by combining immunoregulatory mutations in a candidate vaccine strain...
  22. pmc MyD88 primes macrophages for full-scale activation by interferon-gamma yet mediates few responses to Mycobacterium tuberculosis
    Shuangping Shi
    Graduate Program in Immunology, Graduate School of Medical Sciences, Weill Medical College of Cornell University, Box 62, 1300 York Avenue, New York, NY 10021, USA
    J Exp Med 198:987-97. 2003
    ..Thus, MyD88 plays a dynamic role in resting macrophages that supports IFN-gamma-dependent activation, whereas macrophages can respond to a complex microbial stimulus, the tubercle bacillus, chiefly by other routes...
  23. ncbi request reprint Controlling gene expression in mycobacteria
    Sabine Ehrt
    Weill Medical College of Cornell University, Department of Microbiology and Immunology, Weill Graduate Program in Immunology and Microbial Pathogenesis, Weill Graduate School of Medical Sciences of Cornell University, NY 10021, USA
    Future Microbiol 1:177-84. 2006
    ..This article will review the features of available mycobacterial genetic switches and discuss their applications...
  24. pmc Mycobacterial nonhomologous end joining mediates mutagenic repair of chromosomal double-strand DNA breaks
    Nicolas C Stephanou
    Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    J Bacteriol 189:5237-46. 2007
    ..These findings demonstrate that prokaryotic NHEJ is specifically required for DSB repair in late stationary phase and can mediate mutagenic repair of homing endonuclease-generated chromosomal DSBs...
  25. doi request reprint Mycobacterial genes essential for the pathogen's survival in the host
    Sabine Ehrt
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA
    Immunol Rev 264:319-26. 2015
    ..Here, we review select examples, which exemplify this complexity, highlighting the distinct phases of Mtb's life cycle and the diverse microenvironments encountered therein. ..
  26. doi request reprint Disruption of an M. tuberculosis membrane protein causes a magnesium-dependent cell division defect and failure to persist in mice
    Nichole Goodsmith
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York, United States of America
    PLoS Pathog 11:e1004645. 2015
    ..Together, these data implicate PerM as a novel player in mycobacterial cell division and pathogenesis, and are consistent with the hypothesis that immune activation deprives M. tuberculosis of magnesium. ..
  27. doi request reprint Stressed Mycobacteria Use the Chaperone ClpB to Sequester Irreversibly Oxidized Proteins Asymmetrically Within and Between Cells
    Julien Vaubourgeix
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA
    Cell Host Microbe 17:178-90. 2015
    ..Treatment of tuberculosis might be assisted by drugs that cripple the pathway by which Mtb buffers, sequesters, and asymmetrically distributes IOPs. ..
  28. pmc Target-based identification of whole-cell active inhibitors of biotin biosynthesis in Mycobacterium tuberculosis
    Sae Woong Park
    Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA
    Chem Biol 22:76-86. 2015
    ..Several of the most promising hits were cocrystallized with BioA to provide a framework for future structure-based drug design efforts...
  29. ncbi request reprint Isolation of plasmids from E. coli by alkaline lysis
    Sabine Ehrt
    Department of Microbiology, Weill Medical College of Cornell University, New York, NY, USA
    Methods Mol Biol 235:75-8. 2003
  30. pmc Ancestral antibiotic resistance in Mycobacterium tuberculosis
    Rowan P Morris
    Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford Medical School, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 102:12200-5. 2005
    ..Components of the whiB7 system may serve as attractive targets for the identification of inhibitors that render M. tuberculosis or multidrug-resistant derivatives more antibiotic-sensitive...
  31. pmc Biosynthesis and recycling of nicotinamide cofactors in mycobacterium tuberculosis. An essential role for NAD in nonreplicating bacilli
    Helena I M Boshoff
    Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 283:19329-41. 2008
    ..These studies demonstrate the plasticity of the organism in maintaining NAD levels and establish that the two enzymes of the universal pathway are attractive chemotherapeutic targets for active as well as latent tuberculosis...
  32. ncbi request reprint Mycobacterium tuberculosis virulence: lipids inside and out
    Sabine Ehrt
    Nat Med 13:284-5. 2007
  33. pmc Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program
    Martin I Voskuil
    Beckman Center, Rm 241, Stanford Medical School, Stanford, CA 94305, USA
    J Exp Med 198:705-13. 2003
    ..These data lead to a model postulating that, within granulomas, inhibition of respiration by NO production and O2 limitation constrains M. tuberculosis replication rates in persons with latent tuberculosis...
  34. ncbi request reprint Introduction: genomic approaches in infectious diseases
    Dirk Schnappinger
    Microbes Infect 8:1611-2. 2006
  35. pmc Single-chain Tet transregulators
    Christel Krueger
    Lehrstuhl fur Mikrobiologie, Friedrich Alexander Universitat Erlangen Nurnberg, Staudtstrasse 5, D 91058 Erlangen, Germany
    Nucleic Acids Res 31:3050-6. 2003
    ..The data demonstrate that sc Tet transregulators exhibit the phenotype of their respective dimers and lack functional interference when coexpressed in the same cell...

Research Grants1

  1. Alternative Respiratory Chains of M. tuberculosis
    Dirk Schnappinger; Fiscal Year: 2007
    ..abstract_text> ..