Genomes and Genes
Michael S Glickman
Affiliation: Memorial Sloan-Kettering Cancer Center
- Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis -induced inflammation and virulenceVivek Rao
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
J Clin Invest 116:1660-7. 2006..tuberculosis-induced inflammation and virulence. In addition, cyclopropane stereochemistries on mycolic acids interact directly with host cells to both positively and negatively influence host innate immune activation...
- The mmaA2 gene of Mycobacterium tuberculosis encodes the distal cyclopropane synthase of the alpha-mycolic acidMichael S Glickman
Division of Infectious Diseases, Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
J Biol Chem 278:7844-9. 2003..These results expand our knowledge of the biosynthesis of the Mtb cell envelope and will allow further elucidation of the relationship between Mtb pathogenesis and the fine structure of mycolic acids...
- Mutational analysis of Mycobacterium UvrD1 identifies functional groups required for ATP hydrolysis, DNA unwinding, and chemomechanical couplingKrishna Murari Sinha
Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
Biochemistry 48:4019-30. 2009....
- Mycobacteria exploit three genetically distinct DNA double-strand break repair pathwaysRicha Gupta
Immunology Program Molecular Biology Program, Sloan Kettering Institute, New York, NY 10065, USA
Mol Microbiol 79:316-30. 2011..These findings reveal distinctive features of mycobacterial DSB repair, most notably the dedication of the RecBCD and AdnAB helicase-nuclease machines to distinct repair pathways...
- A dual role for mycobacterial RecO in RecA-dependent homologous recombination and RecA-independent single-strand annealingRicha Gupta
Division of Infectious Diseases, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Nucleic Acids Res 41:2284-95. 2013....
- Mycobacterial nonhomologous end joining mediates mutagenic repair of chromosomal double-strand DNA breaksNicolas 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...
- M. tuberculosis intramembrane protease Rip1 controls transcription through three anti-sigma factor substratesJoseph G Sklar
Immunology Program, Sloan Kettering Institute, New York, NY 10021, USA
Mol Microbiol 77:605-17. 2010....
- AdnAB: a new DSB-resecting motor-nuclease from mycobacteriaKrishna Murari Sinha
Molecular Biology Program, Sloan Kettering Institute, New York, New York 10065, USA
Genes Dev 23:1423-37. 2009..AdnAB is a novel signature of the Actinomycetales taxon. Mycobacteria are exceptional in that they encode both AdnAB and RecBCD, suggesting the existence of alternative end-resecting motor-nuclease complexes...
- Domain requirements for DNA unwinding by mycobacterial UvrD2, an essential DNA helicaseKrishna Murari Sinha
Molecular Biology and Immunology Programs, Sloan Kettering Institute, New York, New York 10065, USA
Biochemistry 47:9355-64. 2008..Attempts to disrupt the M. smegmatis uvrD2 gene were unsuccessful unless a second copy of uvrD2 was present elsewhere in the chromosome, indicating that UvrD2 is essential for growth of M. smegmatis...
- Mycobacterium tuberculosis lacking all mycolic acid cyclopropanation is viable but highly attenuated and hyperinflammatory in miceDaniel Barkan
Division of Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, New York, USA
Infect Immun 80:1958-68. 2012..Taken together, our findings establish the immunomodulatory function of the mycolic acid modification pathway in pathogenesis and buttress this enzyme class as an attractive target for antimycobacterial drug development...
- Redundant function of cmaA2 and mmaA2 in Mycobacterium tuberculosis cis cyclopropanation of oxygenated mycolatesDaniel Barkan
Division of Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
J Bacteriol 192:3661-8. 2010..tuberculosis and indicate a substantial redundancy of function for MmaA2 and CmaA2, the latter of which can function as both a cis and trans cyclopropane synthase for the oxygenated mycolates...
- Site-2 protease substrate specificity and coupling in trans by a PDZ-substrate adapter proteinJessica S Schneider
Immunology Program, Sloan Kettering Institute, New York, NY 10021
Proc Natl Acad Sci U S A 110:19543-8. 2013..Our results support a model of S2P substrate specificity in which a substrate-specific adapter protein tethers the S2P to its substrate while holding the protease inactive through its PDZ domain. ..
- Function of site-2 proteases in bacteria and bacterial pathogensJessica S Schneider
Immunology Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Biomedical Sciences, USA
Biochim Biophys Acta 1828:2808-14. 2013..This article is part of a Special Issue entitled: Intramembrane Proteases. ..
- An improved counterselectable marker system for mycobacterial recombination using galK and 2-deoxy-galactoseDaniel Barkan
Infectious Disease Division, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Gene 470:31-6. 2011..These results establish a new counterselectable marker system for use in mycobacteria that can shorten the time to generate unmarked mutations in M. smegmatis and M. tuberculosis...
- Mycolic acid cyclopropanation is essential for viability, drug resistance, and cell wall integrity of Mycobacterium tuberculosisDaniel Barkan
Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Chem Biol 16:499-509. 2009..These results demonstrate that mycolic acid methyltransferases are a promising antibiotic target and that a family of virulence factors can be chemically inhibited with effects not anticipated from studies of each individual enzyme...
- CarD is an essential regulator of rRNA transcription required for Mycobacterium tuberculosis persistenceChristina L Stallings
Immunology Program, Sloan Kettering Institute, New York, NY 10065, USA
Cell 138:146-59. 2009..These findings highlight a distinct molecular mechanism for regulating rRNA transcription in mycobacteria that is critical for M. tuberculosis pathogenesis...
- The pathways and outcomes of mycobacterial NHEJ depend on the structure of the broken DNA endsJideofor Aniukwu
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Genes Dev 22:512-27. 2008..We conclude that the mechanisms of mycobacterial NHEJ are many and the outcomes depend on the initial structures of the DSBs and the available ensemble of end-processing and end-sealing components, which are not limited to Ku and LigD...
- Structure and function of CarD, an essential mycobacterial transcription factorDevendra B Srivastava
Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY 10065, USA
Proc Natl Acad Sci U S A 110:12619-24. 2013..Thus, CarD uses an unusual mechanism for regulating transcription, sensing the DNA conformation where transcription bubble formation initiates. ..
- Characterization of Mycobacterium smegmatis PolD2 and PolD1 as RNA/DNA polymerases homologous to the POL domain of bacterial DNA ligase DHui Zhu
Molecular Biology Program, Sloan Kettering Institute, New York, NY 10065, USA
Biochemistry 51:10147-58. 2012..Whereas our results document the existence and characteristics of new stand-alone members of the LigD POL family of RNA/DNA polymerases, they imply that other polymerases can perform fill-in synthesis during mycobacterial NHEJ...
- Inhibition of mycobacterial infection by the tumor suppressor PTENGuochang Huang
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
J Biol Chem 287:23196-202. 2012..The relationship of PTEN-PI3K-Akt mTOR status and susceptibility to mycobacterial infection suggests that the interaction of mycobacterial pathogens with cancer cells may be influenced by genetic alterations in the tumor cells...
- Mycobacterial UvrD1 is a Ku-dependent DNA helicase that plays a role in multiple DNA repair events, including double-strand break repairKrishna Murari Sinha
Molecular Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
J Biol Chem 282:15114-25. 2007..The physical and functional interactions of bacterial Ku and UvrD1 highlight the potential for cross-talk between components of nonhomologous end joining and nucleotide excision repair pathways...
- Delayed protection by ESAT-6-specific effector CD4+ T cells after airborne M. tuberculosis infectionAlena M Gallegos
Infectious Diseases Service, Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10032, USA
J Exp Med 205:2359-68. 2008..Our results demonstrate that pathogen-specific Th1 cells can provide protection against inhaled M. tuberculosis, but only after the first week of infection...
- DNA ligase C1 mediates the LigD-independent nonhomologous end-joining pathway of Mycobacterium smegmatisHitesh Bhattarai
Weill Cornell Graduate School of Biomedical Sciences, New York, New York, USA
J Bacteriol 196:3366-76. 2014..These findings define the genetic requirements for a LigD-independent NHEJ pathway in mycobacteria and demonstrate that all enzymatic functions of the LigD protein participate in NHEJ in vivo. ..
- The Rip1 protease of Mycobacterium tuberculosis controls the SigD regulonJessica S Schneider
Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School, New York, New York, USA
J Bacteriol 196:2638-45. 2014..In the absence of Rip1, proteolytic maturation of RsdA is impaired. These findings identify RsdA/SigD as a fourth arm of the branched pathway controlled by Rip1 in M. tuberculosis. ..
- Deficiency of double-strand DNA break repair does not impair Mycobacterium tuberculosis virulence in multiple animal models of infectionBrook E Heaton
Immunology Program, Sloan Kettering Institute, New York, New York, USA
Infect Immun 82:3177-85. 2014..tuberculosis pathogenesis. ..
- Bacterial DNA repair by non-homologous end joiningStewart Shuman
Sloan Kettering Institute, 1275 York Avenue, New York, New York 10021, USA
Nat Rev Microbiol 5:852-61. 2007..Although still a young field, bacterial NHEJ promises to teach us a great deal about the nexus of DNA repair and bacterial pathogenesis...
- Novel imidazoline antimicrobial scaffold that inhibits DNA replication with activity against mycobacteria and drug resistant Gram-positive cocciKendra K Harris
Program in Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, New York 10021, United States
ACS Chem Biol 9:2572-83. 2014..These results identify a new antimicrobial scaffold with a novel mechanism of action and potential therapeutic utility against nonreplicating M. tuberculosis and antibiotic resistant Gram-positive cocci. ..
- The mechanism of action of BCG therapy for bladder cancer--a current perspectiveGil Redelman-Sidi
Sloan Kettering Cancer Center, 1275 York Avenue, Box 9, New York, NY 10065, USA
Nat Rev Urol 11:153-62. 2014..Several gaps still exist in our knowledge that should be addressed in future efforts to understand this biotherapy of cancer. ..
- Oncogenic activation of Pak1-dependent pathway of macropinocytosis determines BCG entry into bladder cancer cellsGil Redelman-Sidi
Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
Cancer Res 73:1156-67. 2013..These results reveal that oncogenic activation of macropinocytosis determines BCG uptake by bladder cancer cells, implying that tumor responsiveness to BCG may be governed by the specific mutations present in the treated cancer cell...
- Converting cancer therapies into cures: lessons from infectious diseasesMichael S Glickman
Infectious Diseases Service and Immunology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
Cell 148:1089-98. 2012..A remaining challenge in both fields is identifying drugs that eliminate drug-tolerant "persister" cells (infectious disease) or tumor-initiating/stem cells (cancer) to prevent late relapse and shorten treatment duration...
- Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector moleculeVivek Rao
Division of Infectious Diseases, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
J Exp Med 201:535-43. 2005....
- Regulation of Mycobacterium tuberculosis cell envelope composition and virulence by intramembrane proteolysisHideki Makinoshima
Immunology Program, Sloan Kettering Institute, New York, New York 10021, USA
Nature 436:406-9. 2005..tuberculosis...
- Site-2 proteases in prokaryotes: regulated intramembrane proteolysis expands to microbial pathogenesisHideki Makinoshima
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
Microbes Infect 8:1882-8. 2006..In this review we will discuss the biochemical functions and physiologic roles of S2P proteases in bacteria and highlight recent data implicating S2P family members in host-pathogen interactions...
- Mechanism of nonhomologous end-joining in mycobacteria: a low-fidelity repair system driven by Ku, ligase D and ligase CChunling Gong
Immunology and Molecular Biology Programs, Sloan Kettering Institute, and Division of Infectious Diseases, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
Nat Struct Mol Biol 12:304-12. 2005..Another ATP-dependent DNA ligase (LigC) provides a backup mechanism for LigD-independent error-prone repair of blunt-end DSBs. We speculate that NHEJ allows mycobacteria to evade genotoxic host defense...
- Crystal structure and nonhomologous end-joining function of the ligase component of Mycobacterium DNA ligase DDavid Akey
Department of Molecular and Cellular Biology, University of California, Berkeley, California 94720, USA
J Biol Chem 281:13412-23. 2006..We surmise that the signature error-prone quality of bacterial NHEJ in vivo arises from a dynamic balance between the end-remodeling and end-sealing steps...
- Efficient allelic exchange and transposon mutagenesis in Mycobacterium avium by specialized transductionJoel Otero
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Appl Environ Microbiol 69:5039-44. 2003..avium. In combination with the forthcoming M. avium genome sequence, these tools will allow the distinct physiologic and pathogenic properties of M. avium to be dissected in molecular detail...
- Crystal structures of mycolic acid cyclopropane synthases from Mycobacterium tuberculosisChih Chin Huang
Department of Biochemistry and Biophysics, Texas A and M University, College Station, Texas 77843 2128, USA
J Biol Chem 277:11559-69. 2002..These structures provide a foundation for rational-drug design, which may lead to the development of new inhibitors effective against persistent bacteria...